INVESTIGADORES
AVILA Cesar Luis
congresos y reuniones científicas
Título:
Multiscale modeling of proteins free energy landscape
Autor/es:
AVILA CL; DRESCHEL NJD; VILLÀ-FREIXA J; CHEHIN, RN
Lugar:
Salta
Reunión:
Congreso; XXXIX Annual Meeting of the Argentinean Biophysical Society and 3rd Latin American Protein Society Meeting; 2010
Resumen:
Several important processes in biology spans different length and time scales. For example, side chain movement can occur at the scale of picoseconds, while loop closure or helix formation (1ns-1µs), β-hairpins folding (1µs-1ms), domain folding (1min-1h) or protein aggregation (1h-years) represent totally different scales and, accordingly, biological problems. Following this, the term "multiscalability" has become an item of intense research, recognizing the need to tackle problems in an integral way, considering the detail that is critical at each level while avoiding expensive exploration of uninteresting regions of the multiple level phase space. In this work we present the implementation of a multiscale method to study the free energy landscape of proteins simulation within ADUN, a multipurpose high performance production molecular simulator. In this approach a simplified coarse-grained model offers an effective way of sampling the landscape. The accuracy of the coarse grain potential is enough to use it as a reference potential for free-energy calculations of different properties of the explicit model. The later is achieved performing a free energy perturbation calculation for the transformation of the coarse-grained to the full atom representation. The procedure represents a smart alternative to brute force and massive computation of uninteresting regions in the all atom potential energy surface. The applicability of the method is illustrated in several examples of protein folding and aggregation.