link.h

药物开发中的基于结构的从头设计代码

# include <stdio.h>
# include <string.h>
# include <stdlib.h>
# include <math.h>
# include <time.h>
# define TRUE 1
# define FALSE 0
# define VDW_1_4_FACTOR 0.50
# define VDW_DIST_CUTOFF 8.00
# define VDW_BUMP_RANGE 0.60
# define MINIMA_ENERGY_CUTOFF 30.00
# define LINK_ENERGY_CUTOFF 100.00
# define ATOM_OVERLAP_RANGE 0.50
# define ANGLE_OVERLAP_RANGE 30.0
# define LOGP_HYDROPHOBIC_CARBON 0.211 
# define LOGP_INTERNAL_HBOND 0.429
# define LOGP_HALOGEN_PAIR 0.137
# define LOGP_NAR_PAIR 0.485
# define LOGP_O3_PAIR -0.268
# define LOGP_ACCEPTOR_PAIR 0.580
# define LOGP_SALICYLIC_ACID 0.554
# define LOGP_AMINO_ACID -2.166
# define HB_ANGLE_CUTOFF 90.0
# define SCORE_VB  -0.168
# define SCORE_MB   0.916
# define SCORE_SHB  0.593
# define SCORE_MHB  0.216
# define SCORE_WHB  0.141
# define SCORE_SWH  0.291
# define SCORE_MWH -0.708
# define SCORE_WWH  0.327
# define SCORE_HM   1.178
# define SCORE_RT  -0.169


class Atom
	{
	 public:
	 	int id;			// ID
		int valid;		// valid indicator
		int part;		// component indicator		
		int num_neib;		// number of neighboring atoms
		int num_nonh;		// number of non-H neighboring atoms
		int neib[10];		// ID of neighboring atoms
		char name[10];		// name of the atom
	 	char type[10];		// SYBYL atom type
	 	char xtype[20];		// SCORE atom type
	 	float coor[3];		// coordinates
		float root[3];		// h-bond roots' coordinates
		float r;		// vdw radius
		float eps;		// vdw epsilon value
		int weight;		// atomic weight
		float R;		// SCORE radius
		float logp;		// atomic hydrophobic scale
		char hb[3];		// h-bond property
	 	float score; 		// atomic binding score
		int ring;		// ring indicator

		Atom();			// constructor
		~Atom();		// deconstructor

		void Show_Content() const;
	};

class Bond
	{
	 public:
		int id;
		int valid;		// valid indicator
		int atom_1;		// ID of the atom_1
		int atom_2;		// ID of the atom_2
		char type[3];		// bond type
		int part;		// ID of the component
		int ring;		// ring indicator
		float length;		// bond length
		int num_neib;		// number of neighboring bonds
		int neib[10];		// ID of neighboring bonds

		Bond();			// constructor
		~Bond();		// deconstructor

		void Show_Content() const;
	};

class Torsion
	{
	 public:
		Atom atom_1;
		Atom atom_2;
		Atom atom_3;
		Atom atom_4;
		char type[3];		// type of the torsion between 2-3
		int angle;		// torsion angle, in degree
		float V;		// potential barrier
		int n;			// periodicity
		int S;			// sign
		float e;		// torsion energy

		Torsion();		// constructor
		~Torsion();		// deconstructor

		void Show_Content() const;
	};

class Group
	{
	 public:
		int valid;
		int num_neib;		// number of neighboring atoms
		int num_nonh;		// number of neighboring non-h atoms
		int num_h;		// number of neighboring hydrogen atoms
		int num_hetero;		// number of neighboring heteroatoms
		int num_pi;		// number of neighboring pi atoms
		int num_car;		// number of neighboring c.ar
		int num_nar;		// number of neighboring n.ar
		int db_type;		// double bond type

		Atom center;		// center atom of the group
		Atom neib[10];		// neighboring atoms
		Bond bond[10];		// bonds

		Group();		// constructor
		~Group();		// deconstructor

		void Show_Content() const;
	};

class Parameter				// diff
        {
         public:
                char seed_file[160];
                char parameter_dir[160];
		char fraglib_dir[160];
		char forbidlib_dir[160];
		char toxiclib_dir[160];
                char pocket_file[160];
                char grid_file[160];

		float grow_ratio;
		float link_ratio;
		float mutate_ratio;

		char apply_chemical_rules[10];
		char apply_forbidden_check[10];
		char apply_toxicity_check[10];

		int max_weight;
		int min_weight;
		float max_logp;
		float min_logp;
		int max_donor;
		int min_donor;
		int max_acceptor;
		int min_acceptor;
		float max_pkd;
		float min_pkd;

		// GA parameters

		int ga_starting_mode;

		int num_generation;
		int max_population;

		char population_file[160];
		char ligands_file[160];

                Parameter(char *filename);
		~Parameter();

		void Read_Index(char *filename);
		void Detect_GA_Start(char *filename);
		void Check_Output();
		void Show_Content() const;
        };

class Pocket
	{
	 private:
                 int num_grid;
                 char *grid;

	 public:
		 int max_x, min_x;      // binding pocket boundary
                 int max_y, min_y;      // binding pocket boundary
                 int max_z, min_z;      // binding pocket boundary

		 int num_atom;
		 Atom *atom;

		 Pocket();	// constructor
		 ~Pocket();	// deconstructor

		 void Show_Content() const;
		 void Read_Grids(char *filename);
		 void Read_Atoms(char *filename);
		 char Get_Grid_Property(float coor[3]) const;
	};

class ForceField
	{
	 private:
		int num_atomtype;
		struct ATOM_DEF
			{
			 char type[10];
			 float r;
			 float eps;
			 int weight;
			};
		ATOM_DEF *atom;

		int num_bondtype;
		struct BOND_DEF
			{
			 char atom_1[10];
			 char atom_2[10];
			 char type[3];
			 float length;
			};
		BOND_DEF *bond;

		int num_torstype;
		struct TORS_DEF
			{
			 char atom_1[10];
			 char atom_2[10];
			 char atom_3[10];
			 char atom_4[10];
			 char type[3];
			 float V;		// twisting force constant
			 int n;			// periodicity
			 int S;			// sign of torsion angle type 
			};
		TORS_DEF *torsion;

		int num_xatomtype;
		struct XATOM_DEF
			{
			 char type[20];
			 float R;
			 int weight;
			 char hb[3];
			 float logp;
			};
		XATOM_DEF *xatom;

	 public:
		ForceField(char *dirname);	// constructor
		~ForceField();			// deconstructor

		void Show_Content() const;
		void Read_ATOM_DEF(char *filename);
		void Read_BOND_DEF(char *filename);
		void Read_TORSION_DEF(char *filename);
		void Read_XATOM_DEF(char *filename);

		void Assign_Atom_Parameters(Atom &atm) const; 
		void Assign_Atom_Xparameters(Atom &atm) const; 
		float Get_Bond_Length(char *a1,char *a2,char *bond_type) const;
		void Assign_Torsion_Parameters(Torsion &tors) const;
		float Cal_Torsion_Energy(Torsion tors) const; 
		float Cal_VDW_Energy(Atom a1,Atom a2,int mark_1_4=FALSE) const; 
	};

class Ligand
        {
         public:
		int id;
		float possibility;	// for building blocks
		int valid;
                char name[80];
                int weight;