Philadelphia (fall 2016)

QM/MM Simulation of Chemical and Biochemical Reaction Pathways: Recent Developments and Applications

Jingzhi Pu (Indiana University–Purdue University Indianapolis), Wei Yang (Florida State University), and Jaili Gao (University of Minnesota)

Combined quantum mechanical/molecular mechanical (QM/MM) simulation methods play a central role in mechanistic understanding of condensed phase reactive processes in complex chemical and biochemical systems. As is generally known, identifying reaction coordinates and mapping reaction pathways with proper statistical sampling are at the core of obtaining thermodynamic and kinetic information to provide mechanistic insights. However, the competing demand for highly accurate QM potentials and adequate statistical sampling has imposed an intrinsic constraint for the approach to be applied to very large-sized systems in a quantitatively reliable manner with commonly available computing resources. Recent years have witnessed exciting progress in both algorithmic developments and computing technologies, which offer promising new directions to tackle the related challenges. These advancements have set a new stage for applying QM/MM simulations to chemical/biological systems with ever increasing complexities. Through this symposium, we would like to gather the major scientists to summarize the progresses and discuss the remaining issues.

Modeling Water and Solvation in Biochemistry: Developments and Applications

Ray Luo (University of California, Irvine) and Emil Alexov (Clemson University)

Biomolecules function in water and their stability, dynamics and interactions are strongly mediated by water. Thus any modeling of biomolecular systems has to account for the solvent effects via strategies that either explicitly or implicitly model water molecules. Hybrid strategies are also developed to balance accuracy and efficiency. The goal of this symposium is to bring together researchers with common interests in developing and utilizing methods for modeling water, solvation, and related electrostatics interactions on biophysical and biochemical properties of proteins, nucleic acids, and their complexes. It is expected that the symposium will forge new collaborations or strengthen ongoing collaborations on common interesting problems. It will reveal the strengths and weaknesses of existing approaches and will help making further improvements. In addition, the symposium will be used to identify important new questions and to guide extension of theoretical and computational models.

Designing Functional Biomaterials: Connecting Experiment with Theory and Simulation

Hung Nguyen (University of California, Irvine) and Jana Shen (University of Maryland)

Advances in processing technologies and our understanding of materials and their properties have made it possible for scientists and engineers to develop more sophisticated biomaterials with targeted functionality. Over the past two decades, much progress has been made in the design, development and fabrication of these materials for a diverse range of applications including medicine, biotechnology and bioelectronics. Theoretical and computational studies exploring structure-property-function relationships are also beginning to emerge. This symposium aims to bring together experimental, theoretical and simulation experts to discuss the state of the art and project future directions as well as to create a cross talk to further advance the field.

Designing Chemical Libraries for Screening

Sourav Das (St. Jude Children's Research Hospital) and Anang Shelat (St. Jude Children's Research Hospital)

Chemical library design is integral to rapid discovery of new chemical compounds in materials design and drug discovery. We invite talks on advances in chemical library design for screening, from both fields. Specific topics of interest include, but not limited to, HTS descriptor application/Topology free approaches in library design, approaches to designing a minimum representative library, network analytics in library design, promiscuity filters, synthetic feasibility filters, inverse QSAR in library design, visualization of libraries and/or chemical space and assessment of impact of practical limitations (e.g. commercial unavailability and synthetic failures) to library design.

Polypharmacology: How little can one afford? How much can you predict?

Dr. Paul Czodrowski (EMD Serono) and Dr. W. Patrick Walters (Vertex Pharmaceuticals)

We plan to organize a mini-symposium that will bring together a number of thought leaders in polypharmacology design and prediction. The methods presented by our suggested speakers cover a wide range from exclusive 2D approaches with a mix of 2D/3D algorithms to the full-fledged comparison of binding pockets.