SCAN: Conformational analysis in a multidimensional energy landscape

SCAN Seminar

Title: Conformational analysis in a multidimensional energy landscape: study of an arginylglutamate

Speaker: Sara Campos - Molecular Simulation Lab

Abstract:

Conformational analysis is an important tool in several areas of molecular modeling, ranging from drug design to protein folding, since it gives insight into the relationship between structural flexibility and function. However, proteins and peptides can adopt a myriad of different conformations, making conformational analysis frequently a difficult task. In addition, the inclusion of pH increases the complexity of these studies by introducing different protonation states. In this work, we develop a method of conformational analysis which is applied to the conformations obtained from molecular dynamics simulations of an arginylglutamate repeat, at different pH values.
Our method starts by finding the conformational coordinates that better preserve the proximity among conformations. Then, the selected set of coordinates is submitted to principal component analysis and the preservation of structural similarity is again assessed with a reduced number of dimensions. We concluded for the need of using a multidimensional (7D/8D) conformation space. Finally, the probability density function and corresponding energy landscape are estimated on that multidimensional space. The analysis of the landscape valleys after applying an energy cutoff, allowed us to group the conformations into distinct and homogeneous classes. Overall, this method was effective in identifying different classes in such a conformational diverse system as the one used in this work.
 

Short CV
2000-2004: Degree in Biochemistry by Faculdade de Ciências e Tecnologia da Universidade de Coimbra.
2005: Research student in the Molecular Simulation group at ITQB, under the supervision of Dr. António M. Baptista.
Since January of 2006: PhD student in the Molecular Simulation group at ITQB, under the supervision of Dr. António M. Baptista. Research area: study of the electrostatic effects on protein structure using computational methods.