We survey the literature on computational methods to predict the pKa of small molecules. In this, we address data availability (used data sets, data quality, proprietary versus public data), molecular representations (quantum mechanics, descriptors, structured representations), prediction methods (...
This is a major factor in the pharmacokinetics of drugs and in the interactions of proteins with other molecules. For both the protein and small molecule cases, we survey the sources of experimental pKa values and then focus on current methods for predicting them. Of particular concern is an ...
Some new drugs are relatively small. Generally, large molecules may increase pharmacokinetic (PK) risks due to low solubility, possibly low cell permeability, increased efflux, and elevated metabolism. During drug discovery/early development, strategies to mitigate some of the risks have included: (i...
A careful selection of the physico-chemical characteristics of the components (molecular weight, hydrogen bonding, pKa, etc.) enables the formation of solvents with different properties (e.g., stability, viscosity, polarity, pH, conductivity, permittivity, and density)14. This aspect is of great ...
Protein–protein interactions dominate all major biological processes in living cells. We have developed a new Monte Carlo-based simulation algorithm to study the kinetic process of protein association. We tested our method on a previously used large ben
Protein interactions constitute an indispensable part of all cellular processes1–6, and strong interactions between protein subunits drive the assembly of permanent molecular machines, such as ATP synthase7–9, and regulate the formation of transient protein complexes in cell signaling pathways10. This...
The continuum solvation models SMD and SM8 were developed using 2,346 solvation free energy values for 318 neutral molecules in 91 solvents as reference. However, no solvation data of neutral solutes in methanol was used in the parametrization, while only few solvation free energy values of solut...
Data fusion approach was investigated in the context of pKa prediction for 391 small molecules derived from a public data source as well as for 681 compounds from an internal corporate database. Four different pKa prediction methods (Simulations Plus ADMET銖剅edictor S+pKa, ACD/Labs Percepta ...
Immune checkpoint inhibitor (ICI) therapy has revolutionised the treatment of various cancer types. ICIs reinstate T-cell function to elicit an anti-cancer immune response. The resulting immune response can however have off-target effects which manifest as autoimmune type serious immune-related adverse...
We present a first-principles calculation and mechanistic characterization of the ion product of liquid water (K W ), based on Quantum Cluster Equilibrium (QCE) theory with a variety of ab initio and density functional methods. The QCE method is based on T-dependent Boltzmann weighting of differ...