Fifth q-bio Summer School: Biomolecules

Description of Theme As system biology thrives to excel in providing cellular level behavior of complex biological systems, it has become imperative to integrate the molecular level events for better understanding at the system level. The objective of this theme is to provide training on computational methodologies to extract molecular level events at different resolutions. In addition we intend to provide a brief review on recent theoretical and computational methods and state-of the-art computing architectures. Finally, we will use examples from our own research to show that the real strength of these computational methodologies can only be materialized when combined with experimental studies. This section of the summer school is organized by "Gnana" S Gnanakaran. Please address all questions about this section of the summer school to its organizer.

Lecturers:

• "Gnana" S Gnanakaran, Los Alamos National Laboratory
• [Partha Ramakrishnan], Los Alamos National Laboratory
• Anurag Sethi, Los Alamos National Laboratory
• Giovanni Bellesia, Los Alamos National Laboratory
• [Jianhui Tian], Los Alamos National Laboratory

Topics:

• Introduction to Computational Structural Biology
• Molecular Modeling Approaches for biomolecular recognition
• Quantum mechanics
• Methods for enzyme catalysis
• Protein Dynamics using Molecular simulation methods
• Molecular communication over long distances using network theory approaches
• Coarse-graining approaches to access biologically relevant time and length scales
• Limitations: Dealing In vivo conditions, Sampling and force fields

Lectures and slides:

• To be announced.

Homework:

• To be announced.

Software:

The students in the spatio-temporal modeling are expected to have the following software installed and working on their laptops for the tutorial sessions in the afternoon.

• VMD [[1]]
• NAMD [[2]]
• C compiler
• CARMA [[3]]

Journal Club Readings:

The papers recommended for the spatio-temporal modeling journal club are listed below. The students will choose an article to present and discuss during the Journal club session.

• Equation of state calculations by fast computing machines. Metropolis et al. Journal of Chemical Physics 21(6), 1087-1092 (1953).

• Understanding modern molecular dynamics: techniques and applications M.E. Tuckerman and G.J. Martyna, Journal of Physical Chemistry B 104(2), 159-178 (2000)

• M. Levitt, A Simplified Representation of Protein Conformations for Rapid Simulation of Protein Folding. J. Mol. Biol. 104, 59-107 (1976)

• D.E. Shaw et al. Atomic-Level Characterization of the Structural Dynamics of Proteins Science 330(6002), 341-346 (2010)

• M.A. Fisher et al. De Novo Designed Proteins from a Library of Artificial Sequences Function in Escherichia Coli and Enable Cell Growth PLoS One 2011, 6(1): e15364

• Y.C. Kim and G. Hummer. Coarse-grained models for simulations of multi-protein complexes Application to ubiquitin binding. J Mol. Biol. 2008, 375:1416-1433

• H Zhou. Quantitative Relation between intermolecule and intramolecular binding to pro-rich peptides to SH3 domains. Biophys. J. 2006, 91: 3170-3181

• P.C. Whitford, et al., Conformational Transitions of Adenylate Kinase: Switching by Cracking. J. Mol. Biol., 2007, 366: 1661-1671.

• S Yang, N.K. Banavali, and B. Roux, Mapping the conformational transition in Src activation by cumulating the information from multiple molecular dynamics trajectories. PNAS, 2009, 106:3776-3781.

• M Karelson and V.S. Lobanov, and A. R. Katritzky Quantum-Chemical Descriptors in QSAR/QSPR Studies Chem. Rev., 1996, 96 (3), pp 1027–1044

• A. Cavalli, P. Carloni, and M. Recanatini, Target-Related Applications of First Principles Quantum Chemical Methods in Drug Design. Chem. Rev., 2006, 106 (9), pp 3497–3519

• M. Lundberg, T. Kawatsu, T. Vreven, M. J. Frisch, and K. Morokuma, Transition States in the Protein Environment -- ONIOM QM:MM Modeling of Isopenicillin N Synthesis,” J. Chem. Theory and Comput., 5 (2009) 222-34.

• K. Morokuma, D. G. Musaev, T. Vreven, H. Basch, M. Torrent and D. V. Khoroshun, "Model studies of the structure, reactivities, and reaction mechanisms of Metalloenzymes," IBM Journal of Research & Development 45(May/July 2001) 367.

• Stabilization and Structure Calculations for Noncovalent Interactions in Extended Molecular Systems Based on Wave Function and Density Functional Theories Kevin E. Riley, Michal Pitok, Petr Jureka, and Pavel Hobza Chem. Rev., 2010, 110 (9), pp 5023–5063

Group Projects

• To be announced.