Molecular Models to Emulate Confinement Effects on the Internal Dynamics of Organophosphorous Hydrolase

• Published in: Advances in Bioinformatics and Computational Biology Vol. 5167; pp. 68 - 78
• Main Authors: Gomes, Diego E. B., Lins, Roberto D., Pascutti, Pedro G., Straatsma, Tjerk P., Soares, Thereza A.
• Format: Book Chapter
• Language: English
• Published: Germany Springer Berlin / Heidelberg 2008; Springer Berlin Heidelberg
• Series: Lecture Notes in Computer Science
• Subjects: atomistic molecular dynamics; enhanced catalytic activity; enzyme im-mobilization; functionalized nanoporous support; phosphotriesterase
• DOI: 10.1007/978-3-540-85557-6_7
• ISBN: 9783540855569; 3540855564
• ISSN: 0302-9743

The confinement of the metalloenzyme organophosphorous hydrolase in functionalized mesoporous silica (FMS) enhances the stability and increases catalytic specific activity by 200% compared to the enzyme in solution. The mechanism by which these processes take place is not well understood. We have developed macroscopic and coarse-grain models of confinement to provide insights into how the nanocage environment steers enzyme conformational dynamics towards enhanced stability and enzymatic activity. The structural dynamics of organophosphorous hydrolase under the two confinement models are very distinct from each other. Comparisons of the present simulations show that only one model leads to an accurate depiction of the internal dynamics of the enzyme.