News & Events


New Paper on an Analytic Model of Alchemical Molecular Binding

posted Nov 12, 2018, 9:45 PM by Emilio Gallicchio

Our work on an analytic model of alchemical molecular binding has been published in the Journal of Chemical Theory and Computation!


The main idea of the model is that the binding free energy, the alchemical free energy profile, the probability distributions of the perturbation energy, and pretty much any thermodynamic observable of the alchemical binding equilibrium can be derived from a single quantity: p0(u), the probability density of the receptor-ligand interaction energy in the ensemble in which they are not interacting. (The concept of asking about the probability of something when that something is not active is weird, but maybe not so weird if you ever thought about alchemical calculations.) Anyway, we set out to develop an analytic model for p0(u) and derived everything else from that. The key here is "analytic", that is a mathematical expression that you can write down on a piece of paper so that all of the derived quantities (binding free energy, free energy profile, perturbation energy distributions, etc.) are all analytic as well. You can then vary the parameters of the model to discover how the properties of the system affect the alchemical equilibrium.

What can you do with that? Well, we are still discovering new ways, but we have already shown that the parameters of the analytic model fit to the data from molecular simulations yield a wealth of information such as the size and flexibility of the receptor binding pocket and the presence of multiple binding modes. We believe that these parameters will be useful as classifiers of molecular complexes. And we are already using the model to optimize the settings of alchemical calculations, such as the lambda schedule. 


Amédée Des Georges talk on cryoEM-based investigation of protein conformational changes

posted Oct 9, 2018, 8:01 AM by Emilio Gallicchio

Amédée Des Georges (City College & ASRC of CUNY) is visiting the Department of Chemistry at Brooklyn College to talk about the latest cryo-EM and image reconstruction technologies to study functional conformational transitions of protein complexes.


Amédée Des Georges

Insights into Ryanodine Receptor Ligand Binding and Gating Using Cryo-EM and Geometric Machine Learning

Wednesday, October 10th, 2018

2:20 pm, Room 133NE Ingersoll Hall


Sci-Mix at Fall ACS Meeting in Boston

posted Aug 27, 2018, 2:57 PM by Emilio Gallicchio   [ updated Aug 27, 2018, 3:09 PM by Rajat Kumar Pal ]

Rajat Pal explains his recent work on the D3 Dopamine Receptor at the Fall ACS Meeting in Boston. His poster has been selected for the Sci-Mix event. Congratulations!

   

Poster on Analytic Model for Molecular Binding at the Fall ACS Meeting in Boston

posted Aug 27, 2018, 2:48 PM by Emilio Gallicchio

Emilio Gallicchio presented a model to extract physical parameters from alchemical binding free energy profiles at the COMP poster session at the Fall ACS Meeting in Boston.

    https://www.dropbox.com/s/093ozi7101s4jy8/poster_analytic_model.pdf?dl=0

Announcing ICoMPUte!

posted Jun 16, 2018, 2:48 PM by Emilio Gallicchio   [ updated Jun 16, 2018, 3:40 PM ]


The Interdisciplinary Computation & Modeling research Program for Undergraduate students (ICoMPUte) will start in September of 2018. It seeks to promote molecular modeling as a research tool in Chemistry and related fields. The program normally lasts two semesters, during which students work in interdisciplinary teams on projects involving wet lab experiments as well as molecular simulations, computer code development, and chemical physics theory & models.

ICoMPUte is managed by the Department of Chemistry at Brooklyn College. A small stipend is provided to qualified students. The program is supported by a generous grant from the National Science Foundation.

Applications are open for the Fall 2018-Spring 2019 session.

Students in laboratory sciences: Chemistry, Biology, Psychology, and Physics as well as Math, Computer Science and Engineering are encouraged to apply. Students interested in chemistry laboratory work are expected to have completed Organic Chemistry II laboratory. Applications from CUNY students not at Brooklyn College are encouraged.

For further questions and eligibility criteria please contact Prof. Emilio Gallicchio, egallicchio@brooklyn.cuny.edu
    

NSF CAREER Award!

posted May 9, 2018, 9:16 AM by Emilio Gallicchio

 





Very exciting news! The Gallicchio's lab will be supported for the next 5 years by a generous CAREER grant from the National Science Foundation for the project: Theory, Models and Computer Simulation of Molecular Recognition Processes.




These resources will support two graduate students while they investigate novel ways to model the thermodynamics of molecular binding processes. One project is aimed at developing a statistical theory to analyze alchemical binding free energy profiles and extract physical parameters of the molecular complexes, characterizing such things as size, shape, energetic complementarity, flexibility, and polarizability. Automated software tools will be employed to obtain physical parameters for a wide range of molecular complexes and machine learning tools will be used to correlate these to chemical and biological properties. In another project, we will develop techniques to deploy large-scale distributed non-equilibrium simulations of molecular binding onto computational grids. We believe that unlocking the tremendous power of computational grids in this fashion will transform the quality and accessibility of atomistic models of molecular recognition. These advances will be collected and shared with the research community by means of high-quality open-source software tools. The robustness and usefulness of these tools will be continuously assessed by applying them to real-world problems in chemical catalysis and medicinal chemistry faced by our partnering experimental laboratories.

We are also very appreciative of the additional generous support we will receive to run a new and exciting interdisciplinary research program for undergraduate students. Students in this program will receive financial support and resources to spend a whole year to deploy both experimental and computational tools to investigate in depth important chemical and biological systems.

We are determined to make the best possible use these precious resources entrusted to us by the NSF. 

Watch out for more news and information about our activities on this channel. Thanks!


Bruce Berne to give the 33rd Friedman Lecture at Brooklyn College

posted Mar 27, 2018, 11:24 AM by Emilio Gallicchio   [ updated Mar 27, 2018, 11:26 AM ]

Professor Bruce Berne, Columbia University, who graduated from Brooklyn College in 1961, will be honored as the host of the 2018 Friedman Lecture at Brooklyn College on April 19th. The annual Friedman Lecture, organized by the Department of Chemistry, is a long-standing tradition at Brooklyn College. Noble laureates such as Hoffman, Taube, Anfinsen, Corey, and Molina are among past honorees. 

Bruce J. Berne was born in Brooklyn, NY. He received his BS in Chemistry from CUNY Brooklyn College in 1961 and his Ph.D. in Chemical Physics from the University of Chicago in 1964. He is currently the Higgins Professor of Chemistry at Columbia University and a member of the National Academy of Sciences. He is known worldwide as one of the pioneers of computer simulations of molecular systems, which are now an integral part of modern Chemical research and the Chemistry curriculum.

The lecture will be held from 1 pm to 2 pm on April 19th, 2018, in the Tanger Auditorium in the Brooklyn College Library building.

https://drive.google.com/open?id=0B6VXyZtFVHc0U0hSUk1GNktZSzVIc1FLNVVyU3o0ZXdEaWUw


A Step Closer to Reliable Modeling of Protein-Peptide Binding

posted Mar 17, 2018, 9:26 PM by Emilio Gallicchio   [ updated Mar 17, 2018, 9:28 PM ]

Congratulations to Denise Kilburg for her paper in Frontiers Molecular Bioscience: Molecular Recognition:



This work moves the field a bit closer to making alchemical calculations of the absolute binding free energies of protein-peptide complexes a reality. It is not at all easy. The first ingredient is to know when things go wrong. And they do ...

Journal Cover of Organic & Biomolecular Chemistry

posted Jan 4, 2018, 7:46 AM by Emilio Gallicchio

Congratulations to students Danielle Hirsch and Rajat Pal whose paper and artistic rendering of an hydroxytropolone bound to an enzyme of the herpes simplex virus has made the journal cover of Organic & Biomolecular Chemistry

http://dx.doi.org/10.1039/C7OB02453C

Release of the AGBNP1 OpenMM Plugin for GPUs

posted Oct 27, 2017, 11:37 AM by Emilio Gallicchio   [ updated Oct 27, 2017, 11:46 AM ]

The AGBNP (Analytic Generalized Born plus Non-Polar) implicit solvent model is our main solvation force field for alchemical binding free energy calculations. Following the development of the GaussVol algorithm for GPUs, we have just completed the implementation of the AGBNP model version 1 on GPUs as part of the OpenMM library. As we reported earlier, the GPU code is up to 100 times faster than our best CPU implementation. While lacking some of the advanced features of AGBNP2 (solvent-excluded volume representation and hydration sites), this milestone moves us closer to a full port of our alchemical binding free energy software stack to GPU devices. The GPU port of AGBNP2 is underway. 


Support from the National Science Foundation is gratefully acknowledged


1-10 of 52