Title

Role of Hydrogen Bonds in Kinematic Mobility and Elasticity Analysis of Protein Molecules

Date of Completion

January 2011

Keywords

Engineering, Mechanical|Biophysics, General|Computer Science

Degree

Ph.D.

Abstract

Biological functions of proteins are facilitated by their three dimensional structures and their ability to shift between these structures (conformational changes). Modeling protein molecules as an open loop kinematic chain of rigid bodies connected by joints provides the foundation for effective approaches to better simulate and understand the structure of protein molecules and their conformational changes. Nevertheless, open loop chain models possess a high number of degrees of freedom (DOF) with considerable computational complications. In addition, real protein molecules appear to exhibit a much lower mobility during the folding process than what is suggested by open loop kinematic models. We propose that the key contributor to the lower mobility of proteins is the formation of hydrogen bonds during the folding process. ^ In this thesis we explore the pivotal role of hydrogen bonds in determining the structure and function of the proteins from the mechanical mobility point of view. We developed a mobility analysis method to determine rigid and flexible regions of protein molecules.^ In addition, hydrogen bonds have a significant role in the mechanical flexibility of the three dimensional structure of protein molecules. In this work hydrogen bonds are modeled as a combination of linear springs with stiffness in all three directions. The stiffness of the proposed element was used in a bottom up approach to define mechanical stiffness of the whole molecule (i.e. its deformation under applied load).^ In particular the main contributions of this work are: 1) Identifying geometric conditions for hydrogen bonds; 2) Kinematic mobility analysis to understand internal mobility of the protein molecule; 3) Reducing degrees of freedom of the open loop kinematic model by the average of 80% while maintaining the actual mobility; 3) Stiffness analysis of hydrogen bonds as flexible mechanical elements in the three dimensional structure of the chain.^ Numerous simulations are also conducted to validate the accuracy and efficiency of the model. ^