rapid sampling of molecular motions with prior information constraints快速采样的分子运动与先验信息约束.pdfVIP

Rapid Sampling of Molecular Motions with Prior Information Constraints 1,2. 2. 1 2 Barak Raveh , Angela Enosh , Ora Schueler-Furman *, Dan Halperin * 1 Department of Molecular Genetics and Biotechnology, Institute of Medical Research, Hadassah Medical School, The Hebrew University, Jerusalem, Israel, 2 School of Computer Science, Tel-Aviv University, Tel Aviv, Israel Abstract Proteins are active, flexible machines that perform a range of different functions. Innovative experimental approaches may now provide limited partial information about conformational changes along motion pathways of proteins. There is therefore a need for computational approaches that can efficiently incorporate prior information into motion prediction schemes. In this paper, we present PathRover, a general setup designed for the integration of prior information into the motion planning algorithm of rapidly exploring random trees (RRT). Each suggested motion pathway comprises a sequence of low-energy clash-free conformations that satisfy an arbitrary number of prior information constraints. These constraints can be derived from experimental data or from expert intuition about the motion. The incorporation of prior information is very straightforward and significantly narrows down the vast search in the typically high-dimensional conformational space, leading to dramatic reduction in running time. To allow the use of state-of-the-art energy functions and conformational sampling, we have integrated this framework into Rosetta, an accurate protocol for diverse types of structural modeling. The suggested framework can serve as an effective complem