October 31, 2019
Surflex Platform version 4.5 has been released. It incorporates the newly introduced eSim methodology as well as recent improvements in the ForceGen approach, particularly for macrocyclic compounds. Please see the Downloads tab.
October 24, 2019
We have just pubished, with Stephen Johnson, a new 3D molecular similarity method (called eSim) that directly incorporates Coulombic field comparison with surface-shape and hydrogen-bonding comparison. It is both faster and more accurate that commonly used alternatives, both for virtual screening and pose prediction. The paper is entitled "Electrostatic-field and surface-shape similarity for virtual screening and pose prediction."
May 25, 2019
We have just pubished a new macrocycle-focused paper with Edward C. Sherer, Mikhail Y. Reibarkh, Qi Gao, Xiao Wang, and Yizhou Liu. The paper is entitled "Complex macrocycle exploration: Parallel, heuristic, and constraint-based conformer generation using ForceGen." Extensive benchmarking results show seconds to minutes conformer elaboration for typical drug-like macrocycles and accurate ensemble generation for large peptidic macrocycles through the use of NMR-based constraints.
January 7, 2019
We have released Surflex Platform version 4.4. This release implements multi-core calculations for ForceGen and QuanSA as well as providing increases in both accuracy and speed of conformer generation.
June 22, 2018
Our paper describing the new QuanSA approach (Quantitative Surface-Field Analysis) has been published in the Journal of Computer-Aided Molecular Design. The method offers a novel mutliple-instance machine-learning methods for binding affinity and pose prediction. It supplants the QMOD method. It is applicable in cases where ligand structure and activity data are available either with or without a crystallographic structure of the protein target. The method is competitive with the FEP approach when structures are available, and the methods have uncorrelated errors, resulting in improved predictions using the approaches in combination.
May 18, 2018
We have released Surflex Platform version 4.3. This release deprecates QMOD in favor of the new QuanSA 3D-QSAR technique and reorganizes functionality among the Surflex modules.
February 14, 2018
We have updated the Surflex Manual to include detailed instructions for running QuanSA. The examples within the full v4.2 rev1 distribution have also been updated to include QuanSA.
January 22, 2018
We have released a minor update to Surflex Version 4.2 (v4.227). Changes include minor bug fixes and speed/quality improvements for conformer elaboration (please see Surflex v4.2 Patch).
January 5, 2018
We have released Surflex Version 4.2. Major improvements have been made with respect to speed in conformer generation and in accuracy particularly for macrocycles. Details of benchmark performance are in a downloadable white paper.
July 4, 2017
We have released Surflex Version 4.1. The four modules (Tools, Dock, Sim, and QMOD) include methods for 2D to 3D structure conversion, conformational elaboration (including efficient macrocycle searching), docking, ligand and protein similarity calculation, off-target prediction, and affinity/binding-pose prediction using either pure structure-activity data or such data augmented with protein structural information.
March 12, 2017
Our paper reporting an entirely new method for 2D to 3D structure generation and conformational elaboration (called ForceGen) has been published in the Journal of Computer-Aided Molecular Design. The method offers better performance on drug-like molecules than competing methods, and it makes macrocyclic ligands tractable both in terms of speed and results quality.
May 25, 2016
Our new QMOD paper reporting extrapolative affinity and pose prediction has been published in the Journal of Computer-Aided Molecular Design. The corresponding software, which includes many improvements in both predictive ability and workflow is available within the Surflex software platform v3.066.
May 25, 2015
We have released a major version upgrade for Surflex-Dock, Surflex-Sim, and Surflex-QMOD (v3.040, QMOD v2.040). This includes the knowledge-guided docking protocol and a deterministic alpha-version of the QMOD methodology.
May 18, 2015
We have just published a paper on a new cross-docking benchmark (called "PINC [PINC Is Not Cognate]") reporting near-cognate level performance on pose prediction using a knowledge-guided docking protocol that combines ensemble docking, ligand similarity, and protein pocket similarity for ensemble composition choice. The paper is published in the Journal of Computer-Aided Molecular Design.
December 8, 2014
We have just published a paper reporting a surprising case of pharmacological crosstalk between the PPAR-alpha transcription factor and the COX enzymes in the Journal of Computer-Aided Molecular Design.
February 14, 2014
We have released a minor version update to Surflex Version 2.7 (now v2.745: see the Downloads page). A small number of bug fixes were made, and robust functionality for protein pocket finding (e.g. in apo structures) has been released as part of the PSIM functionality in Surflex-Dock. Please look at the new Surflex manual for details.
January 23, 2014
We have released Surflex Version 2.7 (see the Downloads page).
New in v2.7 is much faster protein pocket alignment, which is also more general in the way binding site scope is handled. For apo proteins, one can make use of the surflex-dock protomol generator (use the "multicav" specifier mentioned in the manual) to identify cavities. A more general cavity finder, specific to the PSIM-related functionality, will be released in 2014.
Also new in v2.7 is a method for Surflex-Sim that make flexible molecular alignments much faster (roughly 2 million per day on a single computing core). This requires conformation pre-search (using the search_library command), coupled with the use of the -lscreen option. This faster similarity methodology has been integrated into the off-target prediction module (the logodds command), now allowing for much faster profiling of small molecules against sets of other ligands with known biological activities.
November 18, 2013
We have a number of papers recently accepted, to be published shortly. As part of these new reports, the Surflex Platform will undergo a major release in the first quarter of 2014. This will include much faster molecular similarity computations, automatic protein pocket finding and rapid pocket comparison, improvements in docking relating to ligand conformational energetics, and wide release of the QMOD methodology. The Publications tab will be updated when all of the papers have appeared in press electronically.
October 2, 2012
We are pleased to announce the publication of three new papers. The first is a perspective on computer-aided drug design ("Does your model weigh the same as a duck?" in JCAMD). The second is a detailed docking study that was made as part of special symposium from the Spring 2011 ACS ("Surflex-Dock: Docking benchmarks and the real world" also in JCAMD). The third is an exploration of iterative lead optimization using the Surflex-QMOD method ("Iterative refinement of a binding pocket model: Active computational steering of lead optimization" to appear in J. Med. Chem). See the Publications tab for additional details.
November 17, 2011
We have released Surflex version 2.6. The primary changes involve the inclusion of computations for protein pocket similarity (accessed through Surflex-Dock) and for computing log-odds scores of molecules compared with sets of other molecules. These new functions are described in two recent papers (see the Publications tab).
November 10, 2010
We have released Surflex version 2.5. The primary changes are under the hood, but there are significant speed increases, particularly in Surflex-Sim for virtual screening. Typical screening times per molecule, using a single query ligand, are less than one second on the fastest setting (-fscreen) and approximately one second on the standard screening parameters (-pscreen).
September 15, 2010
We have just published a paper addressing a fundamental limitation of most QSAR methods: their lack of physically meaning. By constructing physical active sites for ligand affinity prediction, not only can our QMOD approach produce accurate predictions of affinity and binding mode, it can do so in cases where structure-activity relationships are highly non-additive (see Publications).
March 9, 2010
Dr. Jain is pleased to deliver the OpenEye CUP XI Annual Levinthal Lecture: Molecular Evolution: The Created and the Creators and the Puzzle of Design.
October 24, 2009
We have published two new papers (see Publications tab). The first addresses docking with protein flexibility, and the second introduces a new method to construct binding site models de novo from ligand activity data. The Surflex software corresponding to the first publication is v2.415, now available. The software corresponding to the second paper is still pending release.
December 16, 2008
We have released Surflex Version 2.4, which incorporates the custom scoring function tuning methods decribed in Pham and Jain (2008). This version also includes support for docking to multiple protein conformations. Within the similarity module, additional options have been added to parallel developments with Surflex-Dock. In particular, a new option for fast screening (-fscreen) yields significantly faster times for ligand-based virtual screening.
February 5, 2008
Two methodological papers have been published in a special issue of the Journal of Computer-Aided Molecular Design that relate to methodological performance testing (see the Publications tab). An additional paper describing a method for customization of scoring functions has been published separately. A minor version release of Surflex (v2.2) corresponds to these papers and is available to academic users for download.
April 17, 2007
We have added a Mac version of the Surflex tools to the current (v2.11) distribution. Academic users of the Surflex package may re-download the distribution to gain access. Note that Surflex, fully integrated with SYBYL, is available for commercial use through Tripos Inc. Academics may also obtain a supported and integrated version through Tripos at a substantial discount. The free academic version is unsupported, but we do like to hear about experiences and receive reports of unusual program behavhior (see the Contact tab for an email address).
March 1, 2007
We are pleased to announce the publication of a major new version of Surflex-Dock in the Journal of Computer-Aided Molecular Design (see the Publications tab). The new version, fully integrated with SYBYL, is available for commercial use through Tripos Inc. Academics may also obtain a supported and integrated version through Tripos at a substantial discount. An unsupported academic version is available as well (please see the Contact tab for an email address).