main_link.c

药物开发中的基于结构的从头设计代码

# include "link.h"

// global variables used in this program

Parameter *parm=NULL;		// paramters from the index file
ForceField *ff=NULL;            // force field 
FragLibrary *fraglib=NULL;      // building block library
FragLibrary *forbidlib=NULL;    // forbidden substructure library
FragLibrary *toxiclib=NULL;	// toxic substructure library
Pocket *pok=NULL;		// binding pocket

int main(int argc,char *argv[])
{
	extern Parameter *parm;
	extern ForceField *ff;
	extern FragLibrary *fraglib;
        extern FragLibrary *forbidlib;
	extern FragLibrary *toxiclib;
	extern Pocket *pok;

	if(argc!=2)
		{
		 printf("\n");
		 puts("Error: no index file is given for LINK.");
		 puts("The correct usage is: link index_file");
		 exit(1);
		}

        printf("\nLigBuilder/Link starts to run ... ");
        printf("%s\n",Get_Time());

	Set_Random_Number();

	printf("Now reading parameters from '%s' ... \n", argv[1]);
	Parameter parameter(argv[1]); parm=&parameter;
	// parameter.Show_Content();

	Pocket pocket; pok=&pocket; 
	printf("Now reading the binding pocket grids from '%s' ...\n",parm->grid_file);
	pocket.Read_Grids(parm->grid_file);
	printf("Now reading the binding pocket atoms from '%s' ...\n",parm->pocket_file);
	pocket.Read_Atoms(parm->pocket_file);
	// pocket.Show_Content();

	printf("Now reading force field parameters from '%s' ...\n", parm->parameter_dir); 
	ForceField forcefield(parm->parameter_dir); ff=&forcefield;
	// forcefield.Show_Content();

	printf("Now reading the building block library from '%s' ... \n", parm->fraglib_dir);
	FragLibrary fraglibrary; fraglib=&fraglibrary; 
	fraglibrary.Read_Library(parm->fraglib_dir);
	fraglibrary.Assign_Parameters();
	// fraglibrary.Show_Content();

	FragLibrary forbidlibrary; forbidlib=&forbidlibrary;
	if(!strcmp(parm->apply_forbidden_check,"YES"))
	{	
	 printf("Now reading the forbidden structure library from '%s' ... \n", parm->forbidlib_dir);
	 forbidlibrary.Read_Library(parm->forbidlib_dir);
	 forbidlibrary.Assign_Parameters();
         // forbidlibrary.Show_Content();
	}
        
	FragLibrary toxiclibrary; toxiclib=&toxiclibrary;
	if(!strcmp(parm->apply_toxicity_check,"YES"))
	{
	 printf("Now reading the toxic structure library from '%s' ... \n", parm->toxiclib_dir);
	 toxiclibrary.Read_Library(parm->toxiclib_dir);
	 toxiclibrary.Assign_Parameters();
         // toxiclibrary.Show_Content();
	}

	Population population;
	Ligand seed;
	int i,j;

	printf("\nNow starting the Genetic Algorithm procedure ... ");
	printf("%s\n",Get_Time());
	
	if(parm->ga_starting_mode==1)	// from a seed ligand
		{
		 printf("Now reading the seed structure from '%s' ...\n", parm->seed_file);
		 seed.Read_From_Mol2(parm->seed_file);
		 seed.Detect_Connections();
		 seed.Seed_Structure_Check();
		 seed.Assign_Atom_Parameters();
		 seed.Get_Molecular_Properties();
		 seed.Calculate_Binding_Score();
		 seed.Calculate_Chemical_Score();

		 printf("Now generating the initial population ...\n");
		 population.Initialize(seed);
		 population.Statistics();
        	 population.Count_Wins();
		}
	else 		// from current population
		{
		 printf("Now reading the population from '%s' ...\n", parm->seed_file);
		 population.Read_From_Lig(parm->seed_file);
		 population.Statistics();
        	 population.Count_Wins();
		}

	// GA procedure in steady-state mode 

        int mother_id;
	Ligand result[24];

        for(i=1;i<=parm->num_generation;i++)
                {
                 mother_id=population.Select_A_Mother_Molecule();

                 if(mother_id!=FALSE) 
		{
		 if(population.Growing_On_Molecule(mother_id,result)) 
			{
		 	 // add the new molecules to the population

       		 	 for(j=0;j<24;j++)
               			{
               		 	 if(result[j].valid==0) continue;
			 	 else if(population.Add_A_Molecule_To_Result(result[j])==TRUE)
					{
				 	 result[j].valid=0; 
					 continue;
					}
			 	 else population.Add_A_Molecule_To_Population(result[j]);
                		}
			}
		}

                 if((i%parm->max_population)==0)
                        {
                         printf("\nStatistics of generation %d: ", i);
                         printf("%s",Get_Time());
                         population.Statistics();
                        }
                }

	// now clean up everything

	printf("\nNow saving the final population in '%s' ...\n", parm->population_file);
	population.Write_Out_Lig(parm->population_file);

        printf("\nLigBuilder/Link has done the job successfully ... ");
        printf("%s\n",Get_Time());

	return 0;
}