Modelling protein backbone loops using the Monte Carlo method

Novel methods that perform local moves such as the gaussian bias or Con-<br/>certed Rotation with Angles, increase the exploration of the conformational<br/>phase space. These methods have been applied successfully to small systems,<br/>and have proved to be more efficient than the classical Monte Carlo method.<br/><br/>The main aim of my work was to study and include backbone moves<br/>for proteins, such as the Concerted Rotation with Angle (CRA) and the<br/>gaussian bias in the ProtoMS package. The CRA was then applied to several<br/>systems of biological interest to compute relative binding free energies and<br/>conformational changes to obtain insights into the binding mode and system<br/>flexibility.<br/><br/>The CRA algorithm has been used to sample biological systems such<br/>as lysozyme L99A mutant, Bcr-Abl kinases and PDE5 phosphodiesterase<br/>and led to increased sampling of the backbone and more precise free energy<br/>results.

Name dc:type.qualificationname

Ph.D.

Level dc:type.qualificationlevel

doctoral

Grantor dc:publisher.institution

University of Southampton

Year dc:date.issued

2009

Author dc:creator

• Fernandez-Carmona, Juan

Advisor dc:contributor.advisor

• Essex, Jonathan W.