News & Events

A Novel Surface Area Algorithm for GPUs added to OpenMM

posted Jan 8, 2017, 8:08 AM by Emilio Gallicchio   [ updated Jan 8, 2017, 9:30 AM ]

Surface area of a moleculeAfter a year-long effort, we finally developed an efficient implementation of the Gaussian-based volume and surface area model for GPUs. The work, performed in collaboration with Peter Eastman Vijay Pande at Stanford University, is described in a recent publication to appear in the Journal of Computational Chemistry: 

Baofeng Zhang, Denise Kilburg, Peter Eastman, Vijay S. Pande, Emilio Gallicchio. Efficient Gaussian Density Formulation of Volume and Surface Areas of Macromolecules on Graphical Processing Units. J. Comp. Chem. (2017). pdf of submitted manuscript

Volume and surface area of macromolecules are employed in medicinal chemistry to measure structural similarity and complementarity of compounds. They are also the basis of many implicit models of non-polar solvation, which is our primary interest.

With this algorithm we were able to achieve a 50- to 100-fold speed-up on GPU's relative to our best CPU implementation. more ->

The GaussVol code is freely available on github as a plugin of the OpenMM molecular mechanics package.

Support from the National Science Foundation is gratefully acknowledged

Publication on binding free energy study of RNase H inhibitors

posted Sep 18, 2016, 8:16 AM by Emilio Gallicchio   [ updated Sep 18, 2016, 8:25 AM ]

Our collaboration with the group of Ryan Murelli here at Brooklyn College, and John A Beutler and Stuart F Le Grice at NCI, aimed at identifying  α-hydroxytropolones derivatives capable of inhibiting the RNase H enzyme of the HIV virus is now described in two recent publications (below).

The computational work has been made possible by the WEB computational grid at Brooklyn College maintained by the ITS office at Brooklyn College. Additional computing has been performed on the NSF XSEDE SuperMIC cluster at LSU. Thanks!

Good job done! to Baofeng Zhang who completed his postdoctoral residency in the lab.

Baofeng Zhang, Michael P. D'Erasmo, Ryan P. Murelli, Emilio Gallicchio. Free Energy-Based Virtual Screening and Optimization of RNase H Inhibitors of HIV-1 Reverse Transcriptase. ACS Omega. 2016. pdf of submitted manuscript

Ryan P Murelli, Michael P D'Erasmo, Danielle R Hirsch, C Meck, T Masaoka, JA Wilson, Baofeng Zhang, Rajat K Pal, Emilio Gallicchio, John A Beutler, Stuart F Le Grice. Synthetic α-hydroxytropolones as inhibitors of HIV reverse transcriptase ribonuclease H activity. MedChemComm. 2016. doi:10.1039/C6MD00238B

Support from the National Science Foundation is gratefully acknowledged


posted Sep 7, 2016, 6:20 AM by Emilio Gallicchio   [ updated Sep 7, 2016, 6:24 AM ]

We are happy to announce that a team of CUNY investigators led by our laboratory and including Prof. Lauren Wickstrom (Borough of Manhattan Community College), Prof. Tom Kurtzman (Lehman College), and Prof. Wayne Harding (Hunter College) has been awarded a 1-year Interdisciplinary Research Grant award of $39,500 by the CUNY Office of Research to conduct theoretical and experimental studies of the inhibition of the D3 dopamine receptor:

A Combined Treatment of Hydration and Dynamical Effects for the Modeling of Protein-Ligand Binding Thermodynamics

Summary. The project seeks to develop an improved computational protocol for the study of protein-drug interactions marrying the accuracy of detailed explicit solvation models with the versatility of implicit solvation approaches, and to validate it experimentally on the important D3 dopamine receptor drug target. The work will lead to improved descriptions of the displacement of water molecules from the protein surface and of the dynamical response of molecular conformations upon binding. Current computer models of molecular binding lack in one or both of these critical elements. The primary aim of the project is to exploit the unique and complementary expertise of our team of investigators at CUNY to establish a proof-of-concept base and acquire sufficient preliminary data to compete for federal funding at the national level.

The team will work to develop a custom parameterization of the AGBNP solvation model for the D3 dopamine receptor using accurate Hydration Site Analysis data obtained from explicit solvent simulations. The resulting model will be employed to predict binding constants of a virtual library of D3 inhibitors using the BEDAM alchemical methodology. The most promising identified inhibitors will be synthesized and essayed for binding.  Selective inhibition of the dopamine D3 receptor is a promising therapeutic approach for the treatment of drug abuse disorders. Building on the methodology employed in our recent participation to the SAMPL5 blinded challenge, the project will for the first time attempt to apply a model combining enclosed hydration effects and a dynamical description of binding to a complex protein receptor system.

The award will help fund the research of Rajat Pal, a Ph.D. student in our lab, for the next year. Thanks!

Publication on SAMPL5 host-guest blinded challenge

posted Aug 24, 2016, 12:50 PM by Emilio Gallicchio   [ updated Sep 24, 2016, 9:38 AM ]

Our contribution to the SAMPL5 blinded challenge is now described in a paper to appear in the Journal of Computer Aided Molecular Design:

Rajat Kumar Pal, Kamran Haider, Divya Kaur, William Flynn, Junchao Xia,  Ronald M Levy, Tetiana Taran,* Lauren Wickstrom,  Tom Kurtzman, Emilio Gallicchio. A Combined Treatment of Hydration and Dynamical Effects for the Modeling of Host-Guest Binding Thermodynamics: The SAMPL5 Blinded Challenge. J. Comp. Aided. Mol. Des. 2016. pdf of submitted manuscript *Undergraduate student.

The computational work has been performed on WEB computational grid at Brooklyn College maintained by the ITS office at Brooklyn College, and on the NSF XSEDE SuperMIC cluster at LSU. Thanks!

Support from the National Science Foundation is gratefully acknowledged

Review Paper on Computational Modeling of Protein-Peptide Interactions

posted Aug 24, 2016, 12:48 PM by Emilio Gallicchio

Denise Kilburg has recently completed a review paper summarizing the various methodologies in current use for the modeling of protein-peptide binding with examples of their applications:

Denise Kilburg and Emilio Gallicchio. 
Recent Advances in Computational Models for the Study Protein-Peptide Interactions. Adv. Prot. Chem. Struct. Biol. (2016). pdf of submitted manuscript 

Posters at ACS Sci-Mix

posted Aug 24, 2016, 12:24 PM by Emilio Gallicchio   [ updated Aug 24, 2016, 12:31 PM ]

The posters by Baofeng Zhang and Rajat Pal were selected for the prestigious interdisciplinary Sci-Mix event at the Fall ACS meeting in Philadelphia :

Targeting viral receptors using binding free energy-based virtual screening and GPU-accelerated software

Baofeng Zhang et al.

Abstract:We will describe the GPU-accelerated formulation of our single-decoupling free energy perturbation method for the rapid estimation of absolute binding free energies of protein-ligand complexes. The computational system is based on the OpenMM MD engine and the Asynchronous Replica Exchange job coordination system. While computationally intensive, free energy-based virtual screening can more accurately discriminate binders from non-binders because it includes entropic and conformational reorganization effects in addition to energetic complementarity factors. The method is therefore suitable for the secondary screening of focused ligand libraries, for example to improve on docking enrichment. Because it targets absolute binding free energies, this protocol is useful for preliminary free energy scoring of ligand libraries with diverse scaffolds. We will present examples drawn from recent screening campaigns targeting viral targets with alpha-hydroxytropolone derivatives. The combination of binding free energy predictions with structural analysis of dynamical trajectories has pointed out key aspects which we are currently pursuing to optimize leads and identify novel classes of inhibitors.

Alchemical computational methodologies for the estimation of binding free energies of supramolecular complexes

Rajat Kumar Pal et al.

Abstract:We will review the development and current applications of computational binding free energy protocols based on the alchemical Single-Decoupling Method (SDM) and multi-dimensional Asynchronous Replica Exchange sampling framework (AsyncRE). Asynchronous equilibrium techniques of this kind are particularly suited for heterogeneous computational clusters and computational grids. We have started to explore non-equilibrium approaches which, although inherently less statistically efficient than equilibrium ones, have the advantage of not incurring the overhead of communication between computational threads in a dynamic processing environment. We will describe a novel asynchronous methodology for binding free energy estimation which works under non-equilibrium conditions and requires no exchanges between replicas, thereby leading to higher computational throughput than equilibrium approaches on computational grids. We will present illustrative examples of equilibrium and non-equilibrium calculations drawn from recent investigations of Octa-acid and CBClip host-guest supramolecular complexes. The results indicate that non-equilibrium techniques have the potential to accelerate and streamline binding free energy calculations on computational grids.

Presentation at the Vertex Free Energy Workshop

posted Jun 9, 2016, 12:01 PM by Emilio Gallicchio   [ updated Jun 9, 2016, 12:04 PM ]

This Free Energy Workshop has been held at Vertex's headquarters in Boston last May. It attracts the best practitioners in the area of free energy modeling for biological and pharmaceutical applications. I like it especially because people here are not afraid of exposing problems and challenges. I talked about our latest attempts at employing single-decoupling alchemical transformation to compute the absolute binding free energies of protein-peptide complexes. Slides and animations are below:


YouTube Video

YouTube Video

Presentation on Software & Hardware Technologies at the Spring ACS Meeting in San Diego

posted Mar 17, 2016, 3:20 PM by Emilio Gallicchio

We recently summarized recent progress on software & hardware technologies to study binding processes at the ACS Meeting in San Diego. The pdf of the presentation is below.

SAMPL5 Blinded Challenge

posted Mar 17, 2016, 3:00 PM by Emilio Gallicchio

We recently participated in the SAMPL5 Host-Guest binding blinded challenge. It was an interesting experience and the results are reassuring that our model is physically reasonable. In this edition we partnered with the Kurtzman's lab at Lehman College and Lauren Wickstrom at BMCC to improve the description of enclosed water molecules that get expelled from the host cavity upon ligand binding. Here is  the presentation at the recent D3R/SAMPL5 workshop at UCSD: pdf. The movie in the presentation is shown below. 

YouTube Video

Software Development Research Positions Available

posted Feb 20, 2016, 7:42 AM by Emilio Gallicchio   [ updated Feb 20, 2016, 7:43 AM ]

Two paid research positions for undergraduate students are available in the Computational Molecular Biophysics Laboratory to contribute to a software development project in the area of scientific computing. The positions are suitable for students with familiarity and interest in computer programming. The positions are available immediately (March 2016) continuing for the next five months (July 2016). Contact Prof. Emilio Gallicchio at to schedule an interview. 

Support from the National Science Foundation is gratefully acknowledged

1-10 of 38