INVESTIGADORES
MADRID Marcos Andres
congresos y reuniones científicas
Título:
DIVERGENCE OF PROTEIN STRUCTURE WITH MOLECULAR DYNAMICS SIMULATIONS
Autor/es:
M.A. MADRID; J. ECHAVE
Lugar:
Alejandría, Egipto
Reunión:
Congreso; BioVision Alexandria 2010; 2010
Institución organizadora:
ibliotheca Alexandrina and World Life Sciences Forum
Resumen:
The evolutionary divergence of protein structure is mostly contained within a subspace spanned by the evolving protein’s lowest vibrational normal modes. To gain further insight into the mechanism of protein structural divergence, the group develop the Linearly forced elastic network model (LFENM) that models mutations by adding a linear perturbative term to the coarse grained ENM Hamiltonian of the unperturbed protein. This model shows, for a test case of globins, results wich are in very good agreement with observations and incontrast with tentative biological explanations of previous analysis, predicts that protein structures will evolve along the lowest normal modes even under unselected random mutations, as a result of the chemical physics of the response of elastic networks of oscillators to perturbations. In this work we are using Molecular Dynamics simulation to study the motion of proteins, in particular we carry forward principal component analysis. This involves diagonalization of the covariance matrix of atomic fluctuations to yield collective variables that are sorted according to their contribution to the totalmeansquare fluctuation. Projecting the structural differences betwen couples of proteins onto the eigenvectors of the covariance matrix of one reference protein, we observe a good agreenment with those obtained before. We analyze the structural differences observed not only in homologous (globinlike) proteins but also in unselected experimentally engineered myoglobin mutants and in wildtype variants subject to other perturbations such as ligandbinding and pH changes. We show that the lowest normal modes dominate structural change inall the cases considered and that the PCA made with MD reproduces this behavior quantitatively like LFENM. The collective nature of the lowest normal modes results in global conformational changes that depend little on the exact nature or location of the perturbation.