© 2009 IACS *Corresponding Author Indian J. Phys. 83 (1) 81-90 (2009) Molecular dynamics simulation of HIV-protease with polarizable and non-polarizable force fields B R Meher 1 , M V Satish Kumar 1 and Pradipta Bandyopadhyay 2 * 1 Department of Biotechnology, Indian Institute of Technology, Guwahati-781 039, Assam, India 2 School of Information Technology, Jawaharlal Nehru University, New Delhi-110 067, India E-mail : praban07@gmail.com Received 1 November 2008 accepted 10 December 2008 Abstract : The effect of polarization in biomolecular force field is investigated by performing Molecular Dynamics (MD) simulation of HIV-protease by using two AMBER force fields, namely ff99 (non-polarizable) and ff02 (polarizable). The results of simulation show that the overall structural fluctuation of HIV-protease is reduced in the polarizable simulation. Comparison with the NMR order parameters with the calculated values shows that although some residues are less flexible in the ff02 simulation, the dynamics of two >-hairpins (flaps), the most flexible part of the protein, is relatively insensitive to the effect of polarization. The flap-active site distance, a measure of flap opening, is distinctly more in the non-polarizable simulation. The water count and radial distribution functions are investigated near a representative residue of three types – charged, polar and hydrophobic. Both water count and radial distribution function differ significantly near the charged residue (catalytic Asp25) between the force fields. However, the water movement is similar near the polar (Ser37) and hydrophobic (Ile85) residues. The preliminary results of this investigation show that polarization is likely to influence both global and specific local motions of protein and solvent. Keywords : MD simulation, force field, polarizability, HIV-protease PACS Nos. : 87.15.Aa, 87.15.He 1. Introduction Computer simulation of molecular and biomolecular systems has reached a stage, where problems of immense practical importance can be studied in chemical, biological and material science [1,2]. In biological science, various phenomena at different length and time scales have been studied using different simulation techniques. Some of the interesting examples are simulation of ribosome, ion channel simulation, understanding the mechanism of bacterial flagella [3–5]. In the all-atom simulation of biomolecules, the most prominent tool is molecular