AutoQSAR

AutoQSAR democratizes creation and application of QSAR models through automation, following a best practices QSAR modeling workflow. With AutoQSAR, high-quality, predictive QSAR models can be created and employed with confidence by QSAR experts and non-experts alike. The best practices workflow includes descriptor generation, feature selection, creation of a large number of QSAR models from several methods including kernel-based partial least squares, naive bayes, and ensemble-based recursive partitioning with different training/test set splits, and ranking of QSAR models by performance. Predictions can be made from a consensus of the best models or from a particular model.

BioLuminate

BioLuminate offers a wide range of tools for protein modeling, protein engineering, protein analysis, peptide analysis, and antibody modeling. In addition to the unique tools, BioLuminate provides access to many of the related tools in the Schrödinger software suite. The BioLuminate interface is a customization (profile) of the Maestro interface, designed for protein modeling.

Canvas

Canvas: A comprehensive cheminformatics computing environment Canvas is a powerful suite of cheminformatics tools built on innovative technologies that achieve unmatched performance and versatility. Canvas offers solutions to a wide range of problems faced by researchers with all levels of modeling expertise.

CombiGlide

The Advantages of Computational Lead Optimization The virtual chemical space that chemists are interested in is too large to be synthesized and screened, even using modern methods of combinatorial chemistry and robotic synthesis. Therefore, there is a real need for efficient and reliable methods to rationally select the optimal library members for synthesis. Additionally, once a promising lead compound is discovered, different core scaffolds as well as side-chain substitutions must be enumerated and examined to evaluate relative binding affinities towards a particular target. Accurate ligand-receptor scoring coupled with intelligent and efficient combinatorial docking and core-hopping methods can accelerate lead optimization and aid in designing the optimal, focused compound library for further synthesis. Schroedinger's CombiGlide can flexibly vary the core or side-chain substitutions, creating virtual combinatorial libraries that may be screened for leads, identify novel scaffolds, or generate focused libraries in support of lead optimization efforts.

ConfGen

ConfGen: Accurate and efficient bioactive conformational searching for computer-aided drug design Reproducing bioactive ligand geometries in minimally sized conformer sets, accurate results from high-performance ConfGen calculations save time and effort in downstream applications.

Core Hopping

Core Hopping: Comprehensive ligand- and receptor-based scaffold exploration for lead optimization In addition to more conventional ligand-based methods, Core Hopping offers receptor-based scaffold hopping, exploiting information about the active site and known binding poses to guide the search for novel cores.

Desmond

Desmond: High-performance molecular dynamics simulations for biomolecular systems Desmond's combined speed and accuracy make possible long time scale molecular dynamics simulations, allowing users to examine events of great biological and pharmaceutical importance. Seamlessly integrated with Maestro, Desmond provides comprehensive setup, simulation, and analysis tools.

Epik

The Advantages of Empirical pKa Prediction Proper treatment of ligand protonation states is essential to lead discovery. The pKa's of a drug's various functional groups play a critical role in determining its bioavailability and pharmacokinetic profile, while virtual screening software relies on correctly protonated structures in order to perceive the discrete interactions that drive ligand binding. However, many readily available libraries provide ligand structures in familiar tautomeric forms with all functional groups neutralized. These forms may not be highly populated under biological conditions, and are therefore inappropriate for property prediction or virtual screening experiments. Epik provides a time-tested solution to these problems, designed specifically to work within the context of contemporary drug discovery workflows. Using Hammett and Taft methods in conjunction with ionization and tautomerization tools, Epik is able to rapidly and reliably predict pKa values and return all chemically sensible structures.

FEP+

The Advantages of Free Energy Perturbation Calculations Achieving highly potent binding, while maintaining a host of other ligand properties required for safety and biological efficacy, is a primary objective of small molecule drug discovery. Historically, it has been challenging for free energy calculations to achieve the accuracy, reliability, ease of use, and throughput that are required to impact lead optimization in an industrial setting. Thanks to recent advances in force fields and sampling algorithms, coupled with the availability of low-cost parallel computing, free energy calculations can now yield meaningful comparisons with experimental binding affinities. The confluence of these advances is allowing in silico simulations to contribute to real-life drug discovery efforts by providing better synthesis decisions during lead optimization.

Field-Based QSAR

Field-Based QSAR: Discover and optimize new lead compounds using quantitative predictions of binding-site chemistry Field-Based QSAR opens up new possibilities in ligand-based drug discovery projects. Supplied with an aligned training set of active and inactive compounds, Field-Based QSAR predicts drug activity on the basis of either force fields or Gaussian fields that describe ligand chemistry.

Glide

The widespread use of combinatorial chemistry and high-throughput screening (HTS) in the pharmaceutical and biotechnology industries means that large numbers of compounds can now routinely be investigated for biological activity. However, screening large chemical libraries remains an expensive and time-consuming process, with significant rates of both false positives and false negatives. High-speed computational methods can now enrich the fraction of suitable lead candidates in a chemical database, thereby creating the potential to greatly enhance productivity and dramatically reduce drug development costs. With an ever increasing number of drug discovery projects having access to high-resolution crystal structures of their targets, high-performance ligand-receptor docking is the clear computational strategy of choice to augment and accelerate structure-based drug design.

IFD-MD

The domain of applicability of structure-based drug design (SBDD) is limited by the difficulty of obtaining a reliable receptor-ligand structure. The dominant method of obtaining a structure (x-ray crystallography) is both expensive and time consuming. In some cases such as membrane proteins or GPCR's obtaining a structure would be difficult if not impossible.IFD-MD is able to obtain an accurate structure to use in SBDD more quickly and easily than experimental determination.

Impact

Induced Fit

Induced Fit: A novel method for fast and accurate prediction of ligand induced conformational changes in receptor active sites Schroedinger's innovative method for modeling the conformational changes induced by ligand binding. By merging the predictive power of Prime with the docking and scoring capabilities of Glide, Induced Fit is able to predict active site geometries with remarkable success.

Jaguar

Jaguar is an ab initio quantum chemistry package for both gas and solution phase calculations, with strength in treating metal-containing systems. Jaguar is an essential component of two other Schrödinger products. The program Maestro provides the graphical user interface to Jaguar, and a QM/MM program QSite uses Jaguar as its quantum-chemical engine.

KNIME Extensions

Schrödinger KNIME Extensions are designed to provide a powerful means for researchers to easily develop, validate, and deploy multi-step computational workflows. KNIME has established itself as the leading open-source data pipelining tool, and provides an ideal platform for researchers looking for a way to combine best-of-breed technologies from commercial software, academic programs, and in-house code. Independent of the Schrödinger Extensions, KNIME already incorporates over 100 processing nodes for data manipulation and mining, including the complete set of analysis models from the well-known Weka data-mining environment. Additionally, it includes plug-ins that run R-scripts, giving users access to a vast library of statistical routines. Visualization of results is made possible by means of KNIME nodes that support interactive use of scatter plots, parallel coordinates, and more.

Liaison

The Advantages Of Linear Interaction Approximation Accurate ranking of binding affinities is crucial in the lead optimization phase of pharmaceutical research in order to develop potent, effective drug candidates. Both academic groups and the pharmaceutical industry have invested a great deal of effort to meet this challenge. Several approaches have been developed, ranging from rapid QSAR-based scoring functions to computationally intensive free energy perturbation (FEP) calculations. But none have fully met the needs of researcher and developers. QSAR-type approaches, though rapid, involve many approximations and produce large errors in binding energy predictions. FEP approaches are more accurate, but cannot be used when ligand structures vary significantly. They also incur substantial CPU costs. Linear interaction approximation (LIA) is a way of combining molecular mechanics calculations with experimental data to build a model scoring function for the evaluation of ligand-protein binding free energies. LIA methods strike a perfect balance between accuracy and computational cost.

LigPrep

LigPrep is a robust collection of tools designed to prepare high quality, all-atom 3D structures for large numbers of drug-like molecules, starting with 2D or 3D structures in SD or Maestro format. The resulting structures can be saved in either SD or Maestro format. The simplest use of LigPrep produces a single, low-energy, 3D structure with correct chiralities for each successfully processed input structure. LigPrep can also produce a number of structures from each input structure with various ionization states, tautomers, stereochemistries, and ring conformations, and eliminate molecules using various criteria including molecular weight or specified numbers and types of functional groups present.

LiveDesign

MacroModel

The energy and properties of a chemical system depend on the exact three-dimensional molecular structure. Subtle variations in functional groups can result in dramatic differences in behavior. Force field methods that represent the potential energy of a molecule as simple functions of distances and angles between atoms have proven to be an efficient and effective approach to obtaining accurate relative energies for chemical systems. The efficiency of force field-based calculations allows the exploration of large portions of the conformational space, revealing the detailed relationship between structure and energy. Force field-based molecular modeling is routinely applied to examine molecular conformations, molecular motion, and intermolecular interactions, such as those in a ligand-receptor complex.