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ACS Award for Computers in Chemical and Pharmaceutical Research Honoring H. Bernhard "Berny" Schlegel (sponsored by Accelrys)
G Andres Cisneros (Wayne State University), Mathew Halls (Schrodinger, Inc), Hrant Hratchian (Gaussian, Inc), Richard Lord (Grand Valley State University), Jason Sonnenberg (Stevenson University)
The potential energy surface (PES) provides a central interconnect for the experimentally observed behavior of molecular systems and the theoretical description of that behavior. Indeed, the shape and contour of the PES dictate the structure and dynamics of molecular systems, and most spectroscopies can be studied as a response of the PES to one or more external perturbations. From geometry optimization to ab initio molecular dynamics, the development of efficient PES exploration methods tailored for quantum chemistry have played a crucial role in expanding the applicability and importance of modern computational chemistry in scientific studies. This symposium honors H. Bernhard Schlegel on the occasion of the 30th anniversary of his landmark “Berny Optimization” paper [J. Comp. Chem., 3, pp214-218 (1982)], and will explore the current state of the field. Discussion topics will include new developments in geometry optimization, ground and excited state dynamics, QM/MM energy surface exploration, and novel applications of such techniques for investigating and understanding chemical questions.
Collaborative Drug Discovery for Neglected Diseases
Hanneke Jansen (Novartis AG), Wendy Cornell (Merck & Co, Inc), Y Jane Tseng (National Taiwan University), & Rommie Amaro (University of California, San Diego)
Nanosimulations and Nanoinformatics
Alexander Tropsha (UNC at Chapel Hill)
Protein-ligand interactions: Insights, new tools and applications in drug design
Rama Kondru (Hoffmann-La Roche, Inc), Sung-Sau So (Hoffmann-La Roche, Inc) & Vickie Tsui (Genentech)
A central challenge in structure‐based drug design concerns the quantitative prediction of the binding affinities of ligand molecules to their biological target. This requires comprehensive understanding of protein‐ligand interactions and some recent studies have highlighted the nature of these interactions and their usefulness for drug discovery.[1-3] As the number of high-resolution structures of protein‐ligand complexes in the Protein Data Bank is rapidly increasing, there is a great opportunity to capitalize on this rich data source. However, the computational tools currently available to study protein‐ligand complexes are often cumbersome to use and have only limited functionalities, thereby rendering the task of data‐mining and understanding even simple interaction patterns ineffective. A parallel method to understand these interactions is to improve the accuracy of the underlying physics used for calculating protein-ligand binding affinities. To this end, several groups have active research to better account for solvation effects, improve and evaluate QM/MM methods, as well as study the role of entropy in binding. Despite these progresses, we believe that many fundamental questions remain unanswered. For examples, what are the key interactions that we can exploit for each of the amino acids in the binding site? What are the best ways to place a chemical group (e.g. sulfonamide) within a protein environment? What is optimal filling of the pocket? Why does a magic cyano group exist? Clearly, answers to these questions as well as a thorough understanding of the underlying phenomenon can add significant value to intelligent designs and advance our ability to design better drugs. The goal of this symposium is to bring together the computational chemistry community to discuss and develop an in‐depth understanding of protein‐ligand interactions. Here, a diverse group of scientists can provide their unique insights of how small molecule ligands interact with the protein, why certain interactions are favored or disfavored, and their collective view can eventually lead to some simple guiding principles that will serve as foundational knowledge for structure‐based drug design.
- Systematic investigation of halogen bonding in protein‐ligand interactions. Hardegger et al. Angewandte Chemie, International Edition (2011), 50(1), 314‐318
- Computational methodologies for compound database searching that utilize experimental protein‐ligand interaction information. Tan, et al. Chemical Biology & Drug Design (2010), 76(3), 191‐200
- Ligand binding to protein‐binding pockets with wet and dry regions. Wang, et al. Proceedings of the National Academy of Sciences of the United States of America (2011), 108(4), 1326‐1330
Potential function uncertainty and validation
Kennie Merz (Quantum Theory Project at the University of Florida) and John Faver (Quantum Theory Project at the University of Florida)
Computational Chemistry/Biology is now a well-established field with numerous significant successes to show for several decades of effort. Nonetheless, several challenges remain both from the computational/theoretical and experimental perspective. This symposium will touch on these challenges and ways in which to overcome them in the coming years. The symposium will will touch on the current state-of-the art in potential functions, potential function development and validation, the establishment of error bounds in computational prediction of free energies, the role sampling plays in free energy calculations and prospects for future development. We expect the presentations to focus both on free energies computed using end-point methods and methods based on ensembles.
Theory and computational modeling of coupled transport processes
Shashi P Karna (Army Research Laboratory), Douglas Dudis (Air Force Research Laboratory), & A Todd Yeates (Air Force Research Laboratory)
The number of technological areas requiring an understanding and control of isolated and coupled transport processes are manifold and growing. Examples include charge and mass transport across interfaces in batteries and capacitors; energy, charge and mass transport in photovoltaic systems; thermal and charge transport in thermoelectric devices; plasma generation and control for electric propulsion, and many others. In all cases a detailed understanding of the transport processes at multiple length and time scales, as can be accomplished through computational/theoretical means, could lead to a more rapid development and improved devices. However, the barriers to a meaningful computational and/or theoretical description in such complicated systems are very difficult to surmount.
Electrochemical devices - batteries, capacitors and photovoltaics - are obvious ways to generate and store electrical energy for use in transportation, load leveling and pulsed power applications. Inefficiencies in the processes occurring at the various interfaces in such devices lead to lower conversion efficiencies, lower stored energy or power densities or lower cycle life. A detailed knowledge of these processes might lead to considerable improvements in device performance. Modeling the transport processes here, however, requires coupling of the quantum nature of electron and energy transport with ionic transport and in some cases bulk flow. The multiscale and multidisciplinary natures of these problems place them at the forefront of computational and theoretical capability.
The overall performance of thermoelectric devices is limited by the Carnot efficiency, but practical materials do not come close to approaching Carnot efficiencies. Much room for improvement is available, and the potential impact is difficult to overestimate. This presents significant challenges requiring simultaneous optimization of electrical conductivity, thermal conductivity, and thermopower (Seebeck coefficient). These are generally interlinked in complex ways such that changing one can negatively influence another. Adequate theory and modeling spanning time and length scales could greatly aid in the development of new thermoelectric materials and devices.
Standing Invited Symposia
These are invited symposia or member-contributed symposia that occur at every or alternating national ACS meetings.
Anthony Nicholls (OpenEye Scientific Software) & Geoff Skillman (OpenEye Scientific Software)
The COMP Division of ACS is pleased to announce a new award symposium -- the "Thomas Kuhn Paradigm Shift Award Competition" -- sponsored by OpenEye Scientific Software. In the 1940's, while still a graduate student, Thomas Kuhn wrote a monograph on the nature of scientific revolution that was to become the most influential document on the nature of science of the Twentieth Century. Published in 1962 as 'The Structure of Scientific Revolutions', Kuhn described what he saw as the "essential tension" between established ideas, or paradigms, and the new; scientific progress arose by conflict and not consensus. The "Thomas Kuhn Paradigm Shift Award" is designed as an opportunity for speakers to present views at odds with perceived wisdom, with particular emphasis on application to the science of drug discovery.