Schrodinger, LLC

Lingle Wang

Robert L Abel

Jeremy Robert Greenwood

Sayan Mondal

Sathesh P Bhat

Byungchan Kim

Yuqing Deng

Yujie Wu

Kyle Konze

Teng Lin

A method and system for calculating the free energy difference between a target state and a reference state. The method includes determining one or more intermediate states using a coupling parameter, performing molecular simulations to obtain ensembles of micro-states for each of the system states, and calculating the free energy difference by an analysis of the ensembles of micro-states of the system states. The method can be particularly suited for calculating physical or non-physical transformation of molecular systems such as ring-opening, ring-closing, and other transformations involving bond breaking and/or formation. A soft bond potential dependent on a bond stretching component of the coupling parameter and different from the conventional harmonic potential is used in the molecular simulations of the system states for the bond being broken or formed during the transformation.

Methods and systems for calculating free energy differences using a modified bond stretch potential

A system, device, and method for predicting an active set of compounds that bind to a biomolecular target is disclosed. The system and device contain modules allowing for the prediction of an active set of compounds. A core identification module can identify the core of an initial lead compound. A core hopping module is used to identify potential lead compounds having different cores compared to the core of an initial lead compound. A scoring module can use computational techniques to calculate the relative binding free energy of each identified potential lead compound. An activity prediction module can use the relative binding free energy calculations to predict an active set of compounds that bind to the biomolecular target. Empirical analysis can be used to inform the accuracy and completeness of the predicted active set of compounds.

Methods for predicting an active set of compounds having alternative cores, and drug discovery methods involving the same

Rational drug design with computational free energy difference calculation using a modified bond stretch potential

A method for computing free energy difference between a reference molecule and a target molecule. The target molecule has the common set of atoms Pand a set of atoms P. The method includes applying a potential to restrain an interaction of the additional atomic component from the set of atoms Pwith the common set of atoms Pin the initial state. The method includes determining one or more transition states along a transformation path between the initial state and target state. The method includes scaling the restrain potential correspondingly along the transformation path until the potential becomes zero when a corresponding end state is reached, and calculating the free energy difference between the reference molecule and the target molecule using a value obtained along the transformation path from the initial state to the target state.

Methods and systems for calculating free energy differences using an alchemical restraint potential

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Lingle Wang