calcgradient.cl 34.1 KB
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/*

OCLADock, an OpenCL implementation of AutoDock 4.2 running a Lamarckian Genetic Algorithm
Copyright (C) 2017 TU Darmstadt, Embedded Systems and Applications Group, Germany. All rights reserved.

AutoDock is a Trade Mark of the Scripps Research Institute.

This program is free software; you can redistribute it and/or
modify it under the terms of the GNU General Public License
as published by the Free Software Foundation; either version 2
of the License, or (at your option) any later version.

This program is distributed in the hope that it will be useful,
but WITHOUT ANY WARRANTY; without even the implied warranty of
MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE.  See the
GNU General Public License for more details.

You should have received a copy of the GNU General Public License
along with this program; if not, write to the Free Software
Foundation, Inc., 51 Franklin Street, Fifth Floor, Boston, MA  02110-1301, USA.

*/

/*
#include "calcenergy_basic.h"
*/
// All related pragmas are in defines.h (accesible by host and device code)

void gpu_calc_gradient(	    
				int    dockpars_rotbondlist_length,
				char   dockpars_num_of_atoms,
			    	char   dockpars_gridsize_x,
			    	char   dockpars_gridsize_y,
			    	char   dockpars_gridsize_z,
		 __global const float* restrict dockpars_fgrids, // This is too large to be allocated in __constant 
		            	char   dockpars_num_of_atypes,
		            	int    dockpars_num_of_intraE_contributors,
			    	float  dockpars_grid_spacing,
			    	float  dockpars_coeff_elec,
			    	float  dockpars_qasp,
			    	float  dockpars_coeff_desolv,

                    // Some OpenCL compilers don't allow declaring 
		    // local variables within non-kernel functions.
		    // These local variables must be declared in a kernel, 
		    // and then passed to non-kernel functions.
		    	__local float* genotype,
/*
		   	__local float* energy,
*/
		    	__local int*   run_id,

		    	__local float* calc_coords_x,
		    	__local float* calc_coords_y,
		    	__local float* calc_coords_z,

	             __constant float* atom_charges_const,
                     __constant char*  atom_types_const,
                     __constant char*  intraE_contributors_const,
                     __constant float* VWpars_AC_const,
                     __constant float* VWpars_BD_const,
                     __constant float* dspars_S_const,
                     __constant float* dspars_V_const,
                     __constant int*   rotlist_const,
                     __constant float* ref_coords_x_const,
                     __constant float* ref_coords_y_const,
                     __constant float* ref_coords_z_const,
                     __constant float* rotbonds_moving_vectors_const,
                     __constant float* rotbonds_unit_vectors_const,
                     __constant float* ref_orientation_quats_const

		    // Gradient-related arguments
		    // Calculate gradients (forces) for intermolecular energy
		    // Derived from autodockdev/maps.py
		
		    // "is_enabled_gradient_calc": enables gradient calculation.
		    // In Genetic-Generation: no need for gradients
		    // In Gradient-Minimizer: must calculate gradients
			,
			    int    dockpars_num_of_genes,
	    	    __local float* gradient_inter_x,
	            __local float* gradient_inter_y,
	            __local float* gradient_inter_z,
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		    __local float* gradient_intra_x,
		    __local float* gradient_intra_y,
		    __local float* gradient_intra_z,
	            __local float* gradient_per_intracontributor,
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		    __local float* gradient_genotype			
)

//The GPU device function calculates the energy of the entity described by genotype, dockpars and the liganddata
//arrays in constant memory and returns it in the energy parameter. The parameter run_id has to be equal to the ID
//of the run whose population includes the current entity (which can be determined with blockIdx.x), since this
//determines which reference orientation should be used.
{
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	// Initializing gradients (forces) 
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	// Derived from autodockdev/maps.py
	for (uint atom_id = get_local_id(0);
		  atom_id < dockpars_num_of_atoms;
		  atom_id+= NUM_OF_THREADS_PER_BLOCK) {
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		// Intermolecular gradients
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		gradient_inter_x[atom_id] = 0.0f;
		gradient_inter_y[atom_id] = 0.0f;
		gradient_inter_z[atom_id] = 0.0f;
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		// Intramolecular gradients
		gradient_intra_x[atom_id] = 0.0f;
		gradient_intra_y[atom_id] = 0.0f;
		gradient_intra_z[atom_id] = 0.0f;
	}

	// Intramolecular gradients of contributor pairs 
	for (uint intracontrib_atompair_id = get_local_id(0);
		  intracontrib_atompair_id < dockpars_num_of_intraE_contributors;
		  intracontrib_atompair_id+= NUM_OF_THREADS_PER_BLOCK) {
		gradient_per_intracontributor[intracontrib_atompair_id] = 0.0f;
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	}

	uchar g1 = dockpars_gridsize_x;
	uint  g2 = dockpars_gridsize_x * dockpars_gridsize_y;
  	uint  g3 = dockpars_gridsize_x * dockpars_gridsize_y * dockpars_gridsize_z;


	// ================================================
	// CALCULATE ATOMIC POSITIONS AFTER ROTATIONS
	// ================================================
	for (uint rotation_counter = get_local_id(0);
	          rotation_counter < dockpars_rotbondlist_length;
	          rotation_counter+=NUM_OF_THREADS_PER_BLOCK)
	{
		int rotation_list_element = rotlist_const[rotation_counter];

		if ((rotation_list_element & RLIST_DUMMY_MASK) == 0)	// If not dummy rotation
		{
			uint atom_id = rotation_list_element & RLIST_ATOMID_MASK;

			// Capturing atom coordinates
			float atom_to_rotate[3];

			if ((rotation_list_element & RLIST_FIRSTROT_MASK) != 0)	// If first rotation of this atom
			{
				atom_to_rotate[0] = ref_coords_x_const[atom_id];
				atom_to_rotate[1] = ref_coords_y_const[atom_id];
				atom_to_rotate[2] = ref_coords_z_const[atom_id];
			}
			else
			{
				atom_to_rotate[0] = calc_coords_x[atom_id];
				atom_to_rotate[1] = calc_coords_y[atom_id];
				atom_to_rotate[2] = calc_coords_z[atom_id];
			}

			// Capturing rotation vectors and angle
			float rotation_movingvec[3];

			float quatrot_left_x, quatrot_left_y, quatrot_left_z, quatrot_left_q;
			float quatrot_temp_x, quatrot_temp_y, quatrot_temp_z, quatrot_temp_q;

			if ((rotation_list_element & RLIST_GENROT_MASK) != 0)	// If general rotation
			{
				// Rotational genes in the Shoemake space expressed in radians
				float u1 = genotype[3];
				float u2 = genotype[4];
				float u3 = genotype[5];

				// u1, u2, u3 should be within their valid range of [0,1]
				quatrot_left_q = native_sqrt(1 - u1) * native_sin(PI_TIMES_2*u2); 
				quatrot_left_x = native_sqrt(1 - u1) * native_cos(PI_TIMES_2*u2);
				quatrot_left_y = native_sqrt(u1)     * native_sin(PI_TIMES_2*u3);
				quatrot_left_z = native_sqrt(u1)     * native_cos(PI_TIMES_2*u3);

				rotation_movingvec[0] = genotype[0];
				rotation_movingvec[1] = genotype[1];
				rotation_movingvec[2] = genotype[2];
			}
			else	// If rotating around rotatable bond
			{
				uint rotbond_id = (rotation_list_element & RLIST_RBONDID_MASK) >> RLIST_RBONDID_SHIFT;

				float rotation_unitvec[3];
				rotation_unitvec[0] = rotbonds_unit_vectors_const[3*rotbond_id];
				rotation_unitvec[1] = rotbonds_unit_vectors_const[3*rotbond_id+1];
				rotation_unitvec[2] = rotbonds_unit_vectors_const[3*rotbond_id+2];
				float rotation_angle = genotype[6+rotbond_id]*DEG_TO_RAD;

				rotation_movingvec[0] = rotbonds_moving_vectors_const[3*rotbond_id];
				rotation_movingvec[1] = rotbonds_moving_vectors_const[3*rotbond_id+1];
				rotation_movingvec[2] = rotbonds_moving_vectors_const[3*rotbond_id+2];

				// Performing additionally the first movement which 
				// is needed only if rotating around rotatable bond
				atom_to_rotate[0] -= rotation_movingvec[0];
				atom_to_rotate[1] -= rotation_movingvec[1];
				atom_to_rotate[2] -= rotation_movingvec[2];

				// Transforming torsion angles into quaternions
				// FIXME: add precision choices with preprocessor directives: 
				// NATIVE_PRECISION, HALF_PRECISION, Full precision
				rotation_angle  = native_divide(rotation_angle, 2.0f);
				float sin_angle = native_sin(rotation_angle);
				quatrot_left_q  = native_cos(rotation_angle);
				quatrot_left_x  = sin_angle*rotation_unitvec[0];
				quatrot_left_y  = sin_angle*rotation_unitvec[1];
				quatrot_left_z  = sin_angle*rotation_unitvec[2];
			}

			// Performing rotation
			if ((rotation_list_element & RLIST_GENROT_MASK) != 0)	// If general rotation,
										// two rotations should be performed
										// (multiplying the quaternions)
			{
				// Calculating quatrot_left*ref_orientation_quats_const,
				// which means that reference orientation rotation is the first
				quatrot_temp_q = quatrot_left_q;
				quatrot_temp_x = quatrot_left_x;
				quatrot_temp_y = quatrot_left_y;
				quatrot_temp_z = quatrot_left_z;

				quatrot_left_q = quatrot_temp_q*ref_orientation_quats_const[4*(*run_id)]-
						 quatrot_temp_x*ref_orientation_quats_const[4*(*run_id)+1]-
						 quatrot_temp_y*ref_orientation_quats_const[4*(*run_id)+2]-
						 quatrot_temp_z*ref_orientation_quats_const[4*(*run_id)+3];
				quatrot_left_x = quatrot_temp_q*ref_orientation_quats_const[4*(*run_id)+1]+
						 ref_orientation_quats_const[4*(*run_id)]*quatrot_temp_x+
						 quatrot_temp_y*ref_orientation_quats_const[4*(*run_id)+3]-
						 ref_orientation_quats_const[4*(*run_id)+2]*quatrot_temp_z;
				quatrot_left_y = quatrot_temp_q*ref_orientation_quats_const[4*(*run_id)+2]+
						 ref_orientation_quats_const[4*(*run_id)]*quatrot_temp_y+
						 ref_orientation_quats_const[4*(*run_id)+1]*quatrot_temp_z-
						 quatrot_temp_x*ref_orientation_quats_const[4*(*run_id)+3];
				quatrot_left_z = quatrot_temp_q*ref_orientation_quats_const[4*(*run_id)+3]+
						 ref_orientation_quats_const[4*(*run_id)]*quatrot_temp_z+
						 quatrot_temp_x*ref_orientation_quats_const[4*(*run_id)+2]-
						 ref_orientation_quats_const[4*(*run_id)+1]*quatrot_temp_y;
			}

			quatrot_temp_q = 0 -
					 quatrot_left_x*atom_to_rotate [0] -
					 quatrot_left_y*atom_to_rotate [1] -
					 quatrot_left_z*atom_to_rotate [2];
			quatrot_temp_x = quatrot_left_q*atom_to_rotate [0] +
					 quatrot_left_y*atom_to_rotate [2] -
					 quatrot_left_z*atom_to_rotate [1];
			quatrot_temp_y = quatrot_left_q*atom_to_rotate [1] -
					 quatrot_left_x*atom_to_rotate [2] +
					 quatrot_left_z*atom_to_rotate [0];
			quatrot_temp_z = quatrot_left_q*atom_to_rotate [2] +
					 quatrot_left_x*atom_to_rotate [1] -
					 quatrot_left_y*atom_to_rotate [0];

			atom_to_rotate [0] = 0 -
					  quatrot_temp_q*quatrot_left_x +
					  quatrot_temp_x*quatrot_left_q -
					  quatrot_temp_y*quatrot_left_z +
					  quatrot_temp_z*quatrot_left_y;
			atom_to_rotate [1] = 0 -
					  quatrot_temp_q*quatrot_left_y +
					  quatrot_temp_x*quatrot_left_z +
					  quatrot_temp_y*quatrot_left_q -
					  quatrot_temp_z*quatrot_left_x;
			atom_to_rotate [2] = 0 -
					  quatrot_temp_q*quatrot_left_z -
					  quatrot_temp_x*quatrot_left_y +
					  quatrot_temp_y*quatrot_left_x +
					  quatrot_temp_z*quatrot_left_q;

			// Performing final movement and storing values
			calc_coords_x[atom_id] = atom_to_rotate [0] + rotation_movingvec[0];
			calc_coords_y[atom_id] = atom_to_rotate [1] + rotation_movingvec[1];
			calc_coords_z[atom_id] = atom_to_rotate [2] + rotation_movingvec[2];

		} // End if-statement not dummy rotation

		barrier(CLK_LOCAL_MEM_FENCE);

	} // End rotation_counter for-loop

	// ================================================
	// CALCULATE INTERMOLECULAR GRADIENTS
	// ================================================
	for (uint atom_id = get_local_id(0);
	          atom_id < dockpars_num_of_atoms;
	          atom_id+= NUM_OF_THREADS_PER_BLOCK)
	{
		uint atom_typeid = atom_types_const[atom_id];
		float x = calc_coords_x[atom_id];
		float y = calc_coords_y[atom_id];
		float z = calc_coords_z[atom_id];
		float q = atom_charges_const[atom_id];

		if ((x < 0) || (y < 0) || (z < 0) || (x >= dockpars_gridsize_x-1)
				                  || (y >= dockpars_gridsize_y-1)
						  || (z >= dockpars_gridsize_z-1)){
			
			// Setting gradients (forces) penalties.
			// These are valid as long as they are high
			gradient_inter_x[atom_id] += 16777216.0f;
			gradient_inter_y[atom_id] += 16777216.0f;
			gradient_inter_z[atom_id] += 16777216.0f;
		}
		else
		{
			// Getting coordinates
			int x_low  = (int)floor(x); 
			int y_low  = (int)floor(y); 
			int z_low  = (int)floor(z);
			int x_high = (int)ceil(x); 
			int y_high = (int)ceil(y); 
			int z_high = (int)ceil(z);
			float dx = x - x_low; 
			float dy = y - y_low; 
			float dz = z - z_low;

			// Capturing affinity values
			uint ylow_times_g1  = y_low*g1;
			uint yhigh_times_g1 = y_high*g1;
		  	uint zlow_times_g2  = z_low*g2;
			uint zhigh_times_g2 = z_high*g2;

			// Grid offset
			uint offset_cube_000 = x_low  + ylow_times_g1  + zlow_times_g2;
			uint offset_cube_100 = x_high + ylow_times_g1  + zlow_times_g2;
			uint offset_cube_010 = x_low  + yhigh_times_g1 + zlow_times_g2;
			uint offset_cube_110 = x_high + yhigh_times_g1 + zlow_times_g2;
			uint offset_cube_001 = x_low  + ylow_times_g1  + zhigh_times_g2;
			uint offset_cube_101 = x_high + ylow_times_g1  + zhigh_times_g2;
			uint offset_cube_011 = x_low  + yhigh_times_g1 + zhigh_times_g2;
			uint offset_cube_111 = x_high + yhigh_times_g1 + zhigh_times_g2;

			uint mul_tmp = atom_typeid*g3;

			float cube[2][2][2];
			cube [0][0][0] = *(dockpars_fgrids + offset_cube_000 + mul_tmp);
			cube [1][0][0] = *(dockpars_fgrids + offset_cube_100 + mul_tmp);
			cube [0][1][0] = *(dockpars_fgrids + offset_cube_010 + mul_tmp);
		        cube [1][1][0] = *(dockpars_fgrids + offset_cube_110 + mul_tmp);
		        cube [0][0][1] = *(dockpars_fgrids + offset_cube_001 + mul_tmp);
			cube [1][0][1] = *(dockpars_fgrids + offset_cube_101 + mul_tmp);
                        cube [0][1][1] = *(dockpars_fgrids + offset_cube_011 + mul_tmp);
                        cube [1][1][1] = *(dockpars_fgrids + offset_cube_111 + mul_tmp);

			// -------------------------------------------------------------------
			// Deltas dx, dy, dz are already normalized 
			// (by host/src/getparameters.cpp) in OCLaDock.
			// The correspondance between vertices in xyz axes is:
			// 0, 1, 2, 3, 4, 5, 6, 7  and  000, 100, 010, 001, 101, 110, 011, 111
			// -------------------------------------------------------------------
			/*
			    deltas: (x-x0)/(x1-x0), (y-y0...
			    vertices: (000, 100, 010, 001, 101, 110, 011, 111)        

				  Z
				  '
				  3 - - - - 6
				 /.        /|
				4 - - - - 7 |
				| '       | |
				| 0 - - - + 2 -- Y
				'/        |/
				1 - - - - 5
			       /
			      X
			*/

			// Intermediate values for vectors in x-direction
			float x10, x52, x43, x76;
			float vx_z0, vx_z1;

			// Intermediate values for vectors in y-direction
			float y20, y51, y63, y74;
			float vy_z0, vy_z1;

			// Intermediate values for vectors in z-direction
			float z30, z41, z62, z75;
			float vz_y0, vz_y1;

			// -------------------------------------------------------------------
			// Calculating gradients (forces) corresponding to 
			// "atype" intermolecular energy
			// Derived from autodockdev/maps.py
			// -------------------------------------------------------------------

			// vector in x-direction
			/*
			x10 = grid[int(vertices[1])] - grid[int(vertices[0])] # z = 0
			x52 = grid[int(vertices[5])] - grid[int(vertices[2])] # z = 0
			x43 = grid[int(vertices[4])] - grid[int(vertices[3])] # z = 1
			x76 = grid[int(vertices[7])] - grid[int(vertices[6])] # z = 1
			vx_z0 = (1-yd) * x10 + yd * x52     #  z = 0
			vx_z1 = (1-yd) * x43 + yd * x76     #  z = 1
			gradient[0] = (1-zd) * vx_z0 + zd * vx_z1 
			*/

			x10 = cube [1][0][0] - cube [0][0][0]; // z = 0
			x52 = cube [1][1][0] - cube [0][1][0]; // z = 0
			x43 = cube [1][0][1] - cube [0][0][1]; // z = 1
			x76 = cube [1][1][1] - cube [0][1][1]; // z = 1
			vx_z0 = (1 - dy) * x10 + dy * x52;     // z = 0
			vx_z1 = (1 - dy) * x43 + dy * x76;     // z = 1
			gradient_inter_x[atom_id] += (1 - dz) * vx_z0 + dz * vx_z1;

			// vector in y-direction
			/*
			y20 = grid[int(vertices[2])] - grid[int(vertices[0])] # z = 0
			y51 = grid[int(vertices[5])] - grid[int(vertices[1])] # z = 0
			y63 = grid[int(vertices[6])] - grid[int(vertices[3])] # z = 1
			y74 = grid[int(vertices[7])] - grid[int(vertices[4])] # z = 1
			vy_z0 = (1-xd) * y20 + xd * y51     #  z = 0
			y_z1 = (1-xd) * y63 + xd * y74     #  z = 1
			gradient[1] = (1-zd) * vy_z0 + zd * vy_z1
			*/

			y20 = cube[0][1][0] - cube [0][0][0];	// z = 0
			y51 = cube[1][1][0] - cube [1][0][0];	// z = 0
			y63 = cube[0][1][1] - cube [0][0][1];	// z = 1
			y74 = cube[1][1][1] - cube [1][0][1];	// z = 1
			vy_z0 = (1 - dx) * y20 + dx * y51;	// z = 0
			vy_z1 = (1 - dx) * y63 + dx * y74;	// z = 1
			gradient_inter_y[atom_id] += (1 - dz) * vy_z0 + dz * vy_z1;

			// vectors in z-direction
			/*	
			z30 = grid[int(vertices[3])] - grid[int(vertices[0])] # y = 0
			z41 = grid[int(vertices[4])] - grid[int(vertices[1])] # y = 0
			z62 = grid[int(vertices[6])] - grid[int(vertices[2])] # y = 1
			z75 = grid[int(vertices[7])] - grid[int(vertices[5])] # y = 1
			vz_y0 = (1-xd) * z30 + xd * z41     # y = 0
			vz_y1 = (1-xd) * z62 + xd * z75     # y = 1
			gradient[2] = (1-yd) * vz_y0 + yd * vz_y1
			*/

			z30 = cube [0][0][1] - cube [0][0][0];	// y = 0
			z41 = cube [1][0][1] - cube [1][0][0];	// y = 0
			z62 = cube [0][1][1] - cube [0][1][0];	// y = 1 
			z75 = cube [1][1][1] - cube [1][1][0];	// y = 1
			vz_y0 = (1 - dx) * z30 + dx * z41;	// y = 0
			vz_y1 = (1 - dx) * z62 + dx * z75;	// y = 1
			gradient_inter_z[atom_id] += (1 - dy) * vz_y0 + dy * vz_y1;

			// -------------------------------------------------------------------
			// Calculating gradients (forces) corresponding to 
			// "elec" intermolecular energy
			// Derived from autodockdev/maps.py
			// -------------------------------------------------------------------

			// Capturing electrostatic values
			atom_typeid = dockpars_num_of_atypes;

			mul_tmp = atom_typeid*g3;
			cube [0][0][0] = *(dockpars_fgrids + offset_cube_000 + mul_tmp);
			cube [1][0][0] = *(dockpars_fgrids + offset_cube_100 + mul_tmp);
      			cube [0][1][0] = *(dockpars_fgrids + offset_cube_010 + mul_tmp);
      			cube [1][1][0] = *(dockpars_fgrids + offset_cube_110 + mul_tmp);
		       	cube [0][0][1] = *(dockpars_fgrids + offset_cube_001 + mul_tmp);
		        cube [1][0][1] = *(dockpars_fgrids + offset_cube_101 + mul_tmp);
		        cube [0][1][1] = *(dockpars_fgrids + offset_cube_011 + mul_tmp);
		        cube [1][1][1] = *(dockpars_fgrids + offset_cube_111 + mul_tmp);

			// vector in x-direction
			x10 = cube [1][0][0] - cube [0][0][0]; // z = 0
			x52 = cube [1][1][0] - cube [0][1][0]; // z = 0
			x43 = cube [1][0][1] - cube [0][0][1]; // z = 1
			x76 = cube [1][1][1] - cube [0][1][1]; // z = 1
			vx_z0 = (1 - dy) * x10 + dy * x52;     // z = 0
			vx_z1 = (1 - dy) * x43 + dy * x76;     // z = 1
			gradient_inter_x[atom_id] += (1 - dz) * vx_z0 + dz * vx_z1;

			// vector in y-direction
			y20 = cube[0][1][0] - cube [0][0][0];	// z = 0
			y51 = cube[1][1][0] - cube [1][0][0];	// z = 0
			y63 = cube[0][1][1] - cube [0][0][1];	// z = 1
			y74 = cube[1][1][1] - cube [1][0][1];	// z = 1
			vy_z0 = (1 - dx) * y20 + dx * y51;	// z = 0
			vy_z1 = (1 - dx) * y63 + dx * y74;	// z = 1
			gradient_inter_y[atom_id] += (1 - dz) * vy_z0 + dz * vy_z1;

			// vectors in z-direction
			z30 = cube [0][0][1] - cube [0][0][0];	// y = 0
			z41 = cube [1][0][1] - cube [1][0][0];	// y = 0
			z62 = cube [0][1][1] - cube [0][1][0];	// y = 1 
			z75 = cube [1][1][1] - cube [1][1][0];	// y = 1
			vz_y0 = (1 - dx) * z30 + dx * z41;	// y = 0
			vz_y1 = (1 - dx) * z62 + dx * z75;	// y = 1
			gradient_inter_z[atom_id] += (1 - dy) * vz_y0 + dy * vz_y1;

			// -------------------------------------------------------------------
			// Calculate gradients (forces) corresponding to 
			// "dsol" intermolecular energy
			// Derived from autodockdev/maps.py
			// -------------------------------------------------------------------

			// Capturing desolvation values
			atom_typeid = dockpars_num_of_atypes+1;

			mul_tmp = atom_typeid*g3;
			cube [0][0][0] = *(dockpars_fgrids + offset_cube_000 + mul_tmp);
			cube [1][0][0] = *(dockpars_fgrids + offset_cube_100 + mul_tmp);
      			cube [0][1][0] = *(dockpars_fgrids + offset_cube_010 + mul_tmp);
      			cube [1][1][0] = *(dockpars_fgrids + offset_cube_110 + mul_tmp);
      			cube [0][0][1] = *(dockpars_fgrids + offset_cube_001 + mul_tmp);
      			cube [1][0][1] = *(dockpars_fgrids + offset_cube_101 + mul_tmp);
      			cube [0][1][1] = *(dockpars_fgrids + offset_cube_011 + mul_tmp);
      			cube [1][1][1] = *(dockpars_fgrids + offset_cube_111 + mul_tmp);

			// vector in x-direction
			x10 = cube [1][0][0] - cube [0][0][0]; // z = 0
			x52 = cube [1][1][0] - cube [0][1][0]; // z = 0
			x43 = cube [1][0][1] - cube [0][0][1]; // z = 1
			x76 = cube [1][1][1] - cube [0][1][1]; // z = 1
			vx_z0 = (1 - dy) * x10 + dy * x52;     // z = 0
			vx_z1 = (1 - dy) * x43 + dy * x76;     // z = 1
			gradient_inter_x[atom_id] += (1 - dz) * vx_z0 + dz * vx_z1;

			// vector in y-direction
			y20 = cube[0][1][0] - cube [0][0][0];	// z = 0
			y51 = cube[1][1][0] - cube [1][0][0];	// z = 0
			y63 = cube[0][1][1] - cube [0][0][1];	// z = 1
			y74 = cube[1][1][1] - cube [1][0][1];	// z = 1
			vy_z0 = (1 - dx) * y20 + dx * y51;	// z = 0
			vy_z1 = (1 - dx) * y63 + dx * y74;	// z = 1
			gradient_inter_y[atom_id] += (1 - dz) * vy_z0 + dz * vy_z1;

			// vectors in z-direction
			z30 = cube [0][0][1] - cube [0][0][0];	// y = 0
			z41 = cube [1][0][1] - cube [1][0][0];	// y = 0
			z62 = cube [0][1][1] - cube [0][1][0];	// y = 1 
			z75 = cube [1][1][1] - cube [1][1][0];	// y = 1
			vz_y0 = (1 - dx) * z30 + dx * z41;	// y = 0
			vz_y1 = (1 - dx) * z62 + dx * z75;	// y = 1
			gradient_inter_z[atom_id] += (1 - dy) * vz_y0 + dy * vz_y1;

			// -------------------------------------------------------------------
		}

	} // End atom_id for-loop (INTERMOLECULAR ENERGY)

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	// Inter- and intra-molecular energy calculation
	// are independent from each other, so NO barrier is needed here.
  	// As these two require different operations,
	// they can be executed only sequentially on the GPU.
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	// ================================================
	// CALCULATE INTRAMOLECULAR GRADIENTS
	// ================================================
	for (uint contributor_counter = get_local_id(0);
	          contributor_counter < dockpars_num_of_intraE_contributors;
	          contributor_counter +=NUM_OF_THREADS_PER_BLOCK)
	{
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		// Getting atom IDs
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		uint atom1_id = intraE_contributors_const[3*contributor_counter];
		uint atom2_id = intraE_contributors_const[3*contributor_counter+1];

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		// Calculating address of first atom's coordinates
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		float subx = calc_coords_x[atom1_id];
		float suby = calc_coords_y[atom1_id];
		float subz = calc_coords_z[atom1_id];

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		// Calculating address of second atom's coordinates
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		subx -= calc_coords_x[atom2_id];
		suby -= calc_coords_y[atom2_id];
		subz -= calc_coords_z[atom2_id];

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		// Calculating atomic distance
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		float atomic_distance = native_sqrt(subx*subx + suby*suby + subz*subz)*dockpars_grid_spacing;

		if (atomic_distance < 1.0f)
			atomic_distance = 1.0f;

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		// Calculating gradient contributions
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		if ((atomic_distance < 8.0f) && (atomic_distance < 20.48f))
		{
			// Getting type IDs
			uint atom1_typeid = atom_types_const[atom1_id];
			uint atom2_typeid = atom_types_const[atom2_id];

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			// Calculating van der Waals / hydrogen bond term
			gradient_per_intracontributor[contributor_counter] += native_divide (-12*VWpars_AC_const[atom1_typeid * dockpars_num_of_atypes+atom2_typeid],
									                     native_powr(atomic_distance, 13)
									       		    );
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			if (intraE_contributors_const[3*contributor_counter+2] == 1) {	//H-bond
				gradient_per_intracontributor[contributor_counter] += native_divide (10*VWpars_BD_const[atom1_typeid * dockpars_num_of_atypes+atom2_typeid],
										                     native_powr(atomic_distance, 11)
										                    );
			}
			else {	//van der Waals
				gradient_per_intracontributor[contributor_counter] += native_divide (6*VWpars_BD_const[atom1_typeid * dockpars_num_of_atypes+atom2_typeid],
										                     native_powr(atomic_distance, 7)
										                    );
			}
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			// Calculating electrostatic term
			// http://www.wolframalpha.com/input/?i=1%2F(x*(A%2B(B%2F(1%2BK*exp(-h*B*x)))))
			float upper = DIEL_A*native_powr(native_exp(DIEL_B*DIEL_H*atomic_distance) + DIEL_K, 2) + (DIEL_B)*native_exp(DIEL_B*DIEL_H*atomic_distance)*(DIEL_B*DIEL_H*DIEL_K*atomic_distance + native_exp(DIEL_B*DIEL_H*atomic_distance) + DIEL_K);
		
			float lower = native_powr(atomic_distance, 2) * native_powr(DIEL_A * (native_exp(DIEL_B*DIEL_H*atomic_distance) + DIEL_K) + DIEL_B * native_exp(DIEL_B*DIEL_H*atomic_distance), 2);
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        		gradient_per_intracontributor[contributor_counter] +=  -dockpars_coeff_elec * atom_charges_const[atom1_id] * atom_charges_const[atom2_id] * 
										native_divide (upper, lower);
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// (-8.5525f + native_divide(86.9525f,(1.0f + 7.7839f*native_exp(-0.3154f*atomic_distance))))
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			// Calculating desolvation term
			gradient_per_intracontributor[contributor_counter] += (
									       (dspars_S_const[atom1_typeid] + dockpars_qasp*fabs(atom_charges_const[atom1_id])) * dspars_V_const[atom2_typeid] +
							                       (dspars_S_const[atom2_typeid] + dockpars_qasp*fabs(atom_charges_const[atom2_id])) * dspars_V_const[atom1_typeid]
				        				      ) *
					                       			dockpars_coeff_desolv * -0.07716049382716049 * atomic_distance * native_exp(-0.038580246913580245*native_powr(atomic_distance, 2));
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		}
	} // End contributor_counter for-loop (INTRAMOLECULAR ENERGY)
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	barrier(CLK_LOCAL_MEM_FENCE);
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	// Accumulating gradients of each atom from "gradient_per_intracontributor"
	if (get_local_id(0) == 0) {
		for (uint contributor_counter = 0;
			  contributor_counter < dockpars_num_of_intraE_contributors;
			  contributor_counter ++) {

			// Getting atom IDs
			uint atom1_id = intraE_contributors_const[3*contributor_counter];
			uint atom2_id = intraE_contributors_const[3*contributor_counter+1];

			// Calculating xyz distances in Angstroms
			// between"atom1_id"-to-"atom2_id"
			float subx = (calc_coords_x[atom1_id] - calc_coords_x[atom2_id]) * dockpars_grid_spacing;
			float suby = (calc_coords_y[atom1_id] - calc_coords_y[atom2_id]) * dockpars_grid_spacing;
			float subz = (calc_coords_z[atom1_id] - calc_coords_z[atom2_id]) * dockpars_grid_spacing;

			// Calculating gradients in xyz components.
			// Gradients for both atoms in a single contributor pair
			// have the same magnitude, but opposite directions
			gradient_intra_x[atom1_id] += gradient_per_intracontributor[contributor_counter] * subx;
			gradient_intra_y[atom1_id] += gradient_per_intracontributor[contributor_counter] * suby;
			gradient_intra_z[atom1_id] += gradient_per_intracontributor[contributor_counter] * subz;

			gradient_intra_x[atom2_id] -= gradient_per_intracontributor[contributor_counter] * subx;
			gradient_intra_y[atom2_id] -= gradient_per_intracontributor[contributor_counter] * suby;
			gradient_intra_z[atom2_id] -= gradient_per_intracontributor[contributor_counter] * subz;
		}
	}
	
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	barrier(CLK_LOCAL_MEM_FENCE);

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	// Accumulating inter- and intramolecular gradients
	for (uint atom_cnt = get_local_id(0);
		  atom_cnt < dockpars_num_of_atoms;
		  atom_cnt+= NUM_OF_THREADS_PER_BLOCK) {
		gradient_inter_x[atom_cnt] = gradient_inter_x[atom_cnt] + gradient_intra_x[atom_cnt];
		gradient_inter_y[atom_cnt] = gradient_inter_y[atom_cnt] + gradient_intra_y[atom_cnt];
		gradient_inter_z[atom_cnt] = gradient_inter_z[atom_cnt] + gradient_intra_z[atom_cnt];
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	}


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	barrier(CLK_LOCAL_MEM_FENCE);

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	for (uint gene_cnt = get_local_id(0);
		  gene_cnt < dockpars_num_of_genes;
		  gene_cnt+= NUM_OF_THREADS_PER_BLOCK) {
		gradient_genotype [gene_cnt] = 0.0f;
	}

	barrier(CLK_LOCAL_MEM_FENCE);


	// ------------------------------------------
	// translation-related gradients
	// ------------------------------------------
	if (get_local_id(0) == 0) {
		for (uint lig_atom_id = 0;
			  lig_atom_id<dockpars_num_of_atoms;
			  lig_atom_id++) {
			gradient_genotype [0] += gradient_inter_x[lig_atom_id]; // gradient for gene 0: gene x
			gradient_genotype [1] += gradient_inter_y[lig_atom_id]; // gradient for gene 1: gene y
			gradient_genotype [2] += gradient_inter_z[lig_atom_id]; // gradient for gene 2: gene z
		}
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		/*
		printf("gradient_x:%f\n", gradient_genotype [0]);
		printf("gradient_y:%f\n", gradient_genotype [1]);
		printf("gradient_z:%f\n", gradient_genotype [2]);
		*/
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	}

	// ------------------------------------------
	// rotation-related gradients 
				
	// Transform gradients_inter_{x|y|z} 
	// into local_gradients[i] (with four quaternion genes)
	// Derived from autodockdev/motions.py/forces_to_delta_genes()

	// Transform local_gradients[i] (with four quaternion genes)
	// into local_gradients[i] (with three Shoemake genes)
	// Derived from autodockdev/motions.py/_get_cube3_gradient()
	// ------------------------------------------
	if (get_local_id(0) == 1) {

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		float3 torque_rot = (float3)(0.0f, 0.0f, 0.0f);
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		// center of rotation 
		// In getparameters.cpp, it indicates 
		// translation genes are in grid spacing (instead of Angstroms)
		float about[3];
		about[0] = genotype[0]; 
		about[1] = genotype[1];
		about[2] = genotype[2];
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		// Temporal variable to calculate translation differences.
		// They are converted back to Angstroms here
		float3 r;
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		for (uint lig_atom_id = 0;
			  lig_atom_id<dockpars_num_of_atoms;
			  lig_atom_id++) {
			r.x = (calc_coords_x[lig_atom_id] - about[0]) * dockpars_grid_spacing; 
			r.y = (calc_coords_y[lig_atom_id] - about[1]) * dockpars_grid_spacing;  
			r.z = (calc_coords_z[lig_atom_id] - about[2]) * dockpars_grid_spacing; 
			torque_rot += cross(r, torque_rot);
		}
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		const float rad = 1E-8;
		const float rad_div_2 = native_divide(rad, 2);

		float quat_w, quat_x, quat_y, quat_z;

		// Derived from rotation.py/axisangle_to_q()
		// genes[3:7] = rotation.axisangle_to_q(torque, rad)
		torque_rot = fast_normalize(torque_rot);
		quat_x = torque_rot.x;
		quat_y = torque_rot.y;
		quat_z = torque_rot.z;

		// rotation-related gradients are expressed here in quaternions
		quat_w = native_cos(rad_div_2);
		quat_x = quat_x * native_sin(rad_div_2);
		quat_y = quat_y * native_sin(rad_div_2);
		quat_z = quat_z * native_sin(rad_div_2);

		// convert quaternion gradients into Shoemake gradients 
		// Derived from autodockdev/motion.py/_get_cube3_gradient

		// where we are in cube3
		float current_u1, current_u2, current_u3;
		current_u1 = genotype[3]; // check very initial input Shoemake genes
		current_u2 = genotype[4];
		current_u3 = genotype[5];

		// where we are in quaternion space
		// current_q = cube3_to_quaternion(current_u)
		float current_qw, current_qx, current_qy, current_qz;
		current_qw = native_sqrt(1-current_u1) * native_sin(PI_TIMES_2*current_u2);
		current_qx = native_sqrt(1-current_u1) * native_cos(PI_TIMES_2*current_u2);
		current_qy = native_sqrt(current_u1)   * native_sin(PI_TIMES_2*current_u3);
		current_qz = native_sqrt(current_u1)   * native_cos(PI_TIMES_2*current_u3);

		// where we want to be in quaternion space
		float target_qw, target_qx, target_qy, target_qz;

		// target_q = rotation.q_mult(q, current_q)
		// Derived from autodockdev/rotation.py/q_mult()
		// In our terms means q_mult(quat_{w|x|y|z}, current_q{w|x|y|z})
		target_qw = quat_w*current_qw - quat_x*current_qx - quat_y*current_qy - quat_z*current_qz;// w
		target_qx = quat_w*current_qx + quat_x*current_qw + quat_y*current_qz - quat_z*current_qy;// x
		target_qy = quat_w*current_qy + quat_y*current_qw + quat_z*current_qx - quat_x*current_qz;// y
		target_qz = quat_w*current_qz + quat_z*current_qw + quat_x*current_qy - quat_y*current_qx;// z

		// where we want ot be in cube3
		float target_u1, target_u2, target_u3;

		// target_u = quaternion_to_cube3(target_q)
		// Derived from autodockdev/motions.py/quaternion_to_cube3()
		// In our terms means quaternion_to_cube3(target_q{w|x|y|z})
		target_u1 = target_qy*target_qy + target_qz*target_qz;
		target_u2 = atan2(target_qw, target_qx);
		target_u3 = atan2(target_qy, target_qz);

		// derivates in cube3
		float grad_u1, grad_u2, grad_u3;
		grad_u1 = target_u1 - current_u1;
		grad_u2 = target_u2 - current_u2;
		grad_u3 = target_u3 - current_u3;
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		// empirical scaling
		float temp_u1 = genotype[3];
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		if ((temp_u1 > 1.0f) || (temp_u1 < 0.0f)){
			grad_u1 *= ((1/temp_u1) + (1/(1-temp_u1)));
		}
		grad_u2 *= 4 * (1-temp_u1);
		grad_u3 *= 4 * temp_u1;
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		// set gradient rotation-ralated genotypes in cube3
		gradient_genotype[3] = grad_u1;
		gradient_genotype[4] = grad_u2;
		gradient_genotype[5] = grad_u3;

		/*
		printf("gradient_shoemake_u1:%f\n", gradient_genotype [3]);
		printf("gradient_shoemake_u2:%f\n", gradient_genotype [4]);
		printf("gradient_shoemake_u3:%f\n", gradient_genotype [5]);
		*/
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	}

	if (get_local_id(0) == 2) {

		for (uint rotbond_id = 0;
			  rotbond_id < dockpars_num_of_genes-6;
			  rotbond_id ++) {

			float3 rotation_unitvec;
			rotation_unitvec.x = rotbonds_unit_vectors_const[3*rotbond_id];
			rotation_unitvec.y = rotbonds_unit_vectors_const[3*rotbond_id+1];
			rotation_unitvec.z = rotbonds_unit_vectors_const[3*rotbond_id+2];

			// Torque of torsions
			float3 torque_tor = (float3)(0.0f, 0.0f, 0.0f);

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			// Iterating over each ligand atom
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			for (uint lig_atom_id = 0;
				  lig_atom_id<dockpars_num_of_atoms;
				  lig_atom_id++) {

				// Calculate torque on point "A" 
				// (could be any other point "B" along the rotation axis)
				float3 atom_coords = {calc_coords_x[lig_atom_id], 
					              calc_coords_y[lig_atom_id], 
					              calc_coords_z[lig_atom_id]};

				float3 atom_force  = {gradient_inter_x[lig_atom_id],
					              gradient_inter_y[lig_atom_id],
				                      gradient_inter_z[lig_atom_id]};

				float3 rotation_movingvec;
				rotation_movingvec.x = rotbonds_moving_vectors_const[3*rotbond_id];
				rotation_movingvec.y = rotbonds_moving_vectors_const[3*rotbond_id+1];
				rotation_movingvec.z = rotbonds_moving_vectors_const[3*rotbond_id+2];

				torque_tor = cross((atom_coords-rotation_movingvec), atom_force);
			}

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			// Projecting torque on rotation axis
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			float torque_on_axis = dot(rotation_unitvec, torque_tor);

			// Assignment of gene-based gradient
			gradient_genotype[rotbond_id+6] = torque_on_axis;

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			/*
			printf("gradient_torsion [%u] :%f\n", rotbond_id+6, gradient_genotype [rotbond_id+6]);
			*/
		} // End of iterations over rotatable bonds
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	}

}