Applying Genetic Algorithms and Rotamer Library to study the Molecular Docking of HIV-1 Protease and CDK-2 with ligands

Efficient computational techniques can aid to study of the protein structure allowing diverse applications in many scientific research fields [1]. The knowledge of their 3D structure can be very important in order to know their function and to find other macromolecular partners with whom they may interact. [1][2]. Combining GA, Rotamer Library , Molecular Dynamics and Molecular Dynamics (MD) can be a good method to investigate the folding and docking problems. We are developing a methodology that combines these 4 techniques to do the molecular docking completely flexible. This paper presents the use of Genetic Algorithms (GA) and rotamer library to simulate docking of protein-ligand with interesting results. The problem of the flexible docking is the high computational cost. Consequently, some method and softwares use some kind of approximation or they limit the flexibility of the protein or ligand. The work, described here, combines genetic algorithms and a backbone dependent rotamer library to simulate a partially flexible docking. We treat the ligand and the protein backbone as rigid. The program uses rotamer library to make flexible the side chains of residues that compose the active site and it allows rigid motions (translation a rotation) of the ligands. It is a simple approach that can generate good results and it corresponds to a first step to combine normal modes, genetic algorithms, rotamer library and molecular dynamics to simulate a completely flexible docking. We defined and used the Force Filed described with a van der waals, electrostatic and a term based on the solvent acessible surface for each atom. We use the parameters proposed by Wensson [3] to calculate the solvation term and we use the parameters of the ligands based in the GROMOS96 [2]. The first step of the methodology is to generate a set of rotamer for the amino acids presents in the active site. This is done from the