Computer Modeling and Molecular Dynamics Simulation Of Angiogenins And Its Ligand Bound Complexes

Abstract

Computational structural biology

Even with rapid advances in structure determination methods, there is a long gap to be bridged between the number of proteins that have been sequenced and the number whose three-dimensional structures have been experimentally elucidated. Experimentally protein structures are determined by X-ray crystallography or by nuclear magnetic resonance spectroscopy (NMR). X-ray crystal structures give a time averaged picture but little information on conformational dynamics. Though NMR gives dynamical information, the technique cannot be applied to systems whose molecular weight is large. Only small proteins fall within the ken of NMR experiments. In most cases the three dimensional structure of the protein alone cannot give a complete picture of its mechanism. It is also essential to know the interactions of proteins with other proteins, with their ligands and substrates in order to have a better understanding of their functioning.

Computer modeling and simulations are now indispensable supplements to experimental structural biology. The last word in protein structure prediction method is far from being said but the ever-improving homology and ab-initio modeling methods give rise to optimism that sometime in the near future these methods will become almost as reliable as experimental techniques. Ligand docking onto protein molecules is as challenging a problem as protein structure predicting itself. Computer modeling methods to dock ligands have to search a wide region of conformational space besides taking into consideration issues of charge and shape complementarities.