Alladi Ramakrishnan Hall

Metal ion induced conformational change and electronic redistribution in proteins: Insights from MD simulations and QM calculations

Dr Samapan Sikdar

IMSc

Bio-molecules such as proteins form complexes with various ligands like, metal ions, peptides and other proteins to govern cellular functions. Metal ion binding often induces conformational change as well as cause electronic redistribution. The conformational free energy and entropy changes are estimated
using histograms of dihedral angles sampled from equilibrium trajectories of all atom molecular dynamics simulation of the protein in free (apo-protein) and bound (holo-protein) states. The conformational thermodynamic changes provide a generalized framework to characterize and distinguish different
conformational states and predict ligand binding sites based on destabilized and disordered residues of biomolecules. The dynamic response of conformational change is characterized through dihedral autocorrelation function in time domain, indicating how the fluctuations are correlated over time and yields characteristic different time-scales of dihedral relaxation in apo- and holo-proteins. The metal ion induced electron redistribution is studied for Ca2+ ion binding sites in a protein through quantum mechanical (QM) calculations in vacuum, implicit and explicit solvent. The QM calculations elucidate role of different residues in providing coordination stability and their functional implications in agreement to experiments. Further, these studies highlight the importance of modelling surrounding solvent medium in terms of accurately describing polarization effects for understanding of protein functions.