May 2, 2017

Molecular Simulation

Molecular simulation uses powerful computers to simulate the interactions between atoms to understand the properties of materials. Such simulations require methods that range from very detailed quantum mechanical calculations on a hand-full of atoms to coarse-grained classical dynamics of large groups of molecules on a timescale of milliseconds or longer. Here are examples of the Molecular Simulation work done at CBIB.

Conformational changes in TRPV1 mediated by Capsaicin (red), generate pore opening by disrupting a hydrophobic seal formed by Ile679.

The perception of pain is mediated by sensing different signals detected by neuronal terminals. The neurons are responsible for integrating noxious stimuli called “nociceptors” which are located within of peripherical neurons terminals. TRPV1 receptor is one of the molecular mechanisms involved in pain stimuli integration and a prominent target for analgesics development. This ion channel is activated by capsaicin, pungent compound found in chili peppers, and several noxious stimuli as high temperature, low pH, endogen, exogen molecules, among others. In this trajectory, we observe the TRPV1 aperture mediated by capsaicin (red) and the phospholipid PIP2 (yellow). The TRPV1 aperture leads the disruption of four isoleucines, which allows waters and ions to pass through the channel.

Poblete, Horacio, Ingrid Oyarzún, Pablo Olivero, Jeffrey Comer, Matías Zuñiga, Romina V Sepúlveda, David Báez-Nieto, Carlos González Leon, Fernando Gonzalez-Nilo, and Ramon Latorre. “Molecular Determinants of Phosphatidylinositol 4,5-Bisphosphate (PI(4,5)P 2) Binding to Transient Receptor Potential V1 (TRPV1) Channels.” The Journal of Biological Chemistry 290, no. 4 (January 22, 2015): 2086–98. doi:10.1074/jbc.M114.613620.