High accuracy quantum-chemistry-based calculation and blind prediction of macroscopic pKa values in the context of the SAMPL6 challenge

Journal of Computer-aided Molecular Design
Philipp PrachtStefan Grimme

Abstract

Recent advances in the development of low-cost quantum chemical methods have made the prediction of conformational preferences and physicochemical properties of medium-sized drug-like molecules routinely feasible, with significant potential to advance drug discovery. In the context of the SAMPL6 challenge, macroscopic pKa values were blindly predicted for a set of 24 of such molecules. In this paper we present two similar quantum chemical based approaches based on the high accuracy calculation of standard reaction free energies and the subsequent determination of those pKa values via a linear free energy relationship. Both approaches use extensive conformational sampling and apply hybrid and double-hybrid density functional theory with continuum solvation to calculate free energies. The blindly calculated macroscopic pKa values were in excellent agreement with the experiment.

References

Sep 15, 1988·Physical Review A: General Physics·A D Becke
Jun 15, 1986·Physical Review. B, Condensed Matter·J P Perdew
Oct 28, 1996·Physical Review Letters·J P PerdewM Ernzerhof
Oct 8, 2005·Journal of Computational Chemistry·Jay L BanksRonald M Levy
Oct 20, 2005·Journal of Computational Chemistry·Frank Eckert, Andreas Klamt
Oct 4, 2007·Journal of Chemical Information and Modeling·Francesca MillettiGabriele Cruciani
Jan 25, 2008·Journal of Medicinal Chemistry·Anthony NichollsVijay S Pande
Mar 4, 2009·The Journal of Physical Chemistry. B·Aleksandr V MarenichDonald G Truhlar
Mar 11, 2009·The Journal of Physical Chemistry. B·David L MobleyKen A Dill
Nov 26, 2009·Chemistry & Biodiversity·Gabriele CrucianiLaura Goracci
Apr 2, 2010·Journal of Computer-aided Molecular Design·Raphael F RibeiroDonald G Truhlar
Apr 8, 2010·Journal of Computer-aided Molecular Design·Pavel V Klimovich, David L Mobley
May 11, 2010·Journal of Computer-aided Molecular Design·Matthew T GeballePeter J Taylor
Oct 15, 2010·The Journal of Chemical Physics·Dmitrij Rappoport, Filipp Furche
Mar 4, 2011·Journal of Computational Chemistry·Stefan GrimmeLars Goerigk
Apr 6, 2012·Journal of Computer-aided Molecular Design·Matthew T Geballe, J Peter Guthrie
Jul 12, 2012·Chemistry : a European Journal·Stefan Grimme
Apr 10, 2013·Biochimica Et Biophysica Acta·James T MuckermanYuko Wasada-Tsutsui
Nov 19, 2013·PeerJ·Martin Peter AnderssonSusan Louise Svane Stipp
Mar 13, 2014·Journal of Computer-aided Molecular Design·David L MobleyJ Peter Guthrie
Jan 31, 2015·The Journal of Physical Chemistry. a·Andreas Klamt, Michael Diedenhofen
Jun 9, 2015·Journal of Chemical Information and Modeling·Peter GedeckFranco Lombardo
Aug 10, 2015·The Journal of Chemical Physics·Stefan GrimmeAndreas Hansen
Sep 8, 2016·PeerJ·Jimmy C KromannJan H Jensen
Sep 30, 2016·Journal of Computer-aided Molecular Design·Caitlin C BannanDavid L Mobley
Jul 25, 2017·The Journal of Chemical Physics·Eike CaldeweyherStefan Grimme
Sep 2, 2017·Journal of Computational Chemistry·Philipp PrachtStefan Grimme

❮ Previous
Next ❯

Citations

Nov 28, 2019·Journal of Computer-aided Molecular Design·Christoph LoschenAndreas Klamt
Feb 14, 2020·Journal of Computer-aided Molecular Design·M R GunnerJohn D Chodera
Feb 20, 2020·Physical Chemistry Chemical Physics : PCCP·Philipp PrachtStefan Grimme
Feb 1, 2020·Journal of Computer-aided Molecular Design·Samarjeet Prasad, Bernard R Brooks
Aug 18, 2020·Journal of Computer-aided Molecular Design·Anikó UdvarhelyiRainer Wilcken
Feb 1, 2019·Journal of Molecular Modeling·Niraj VermaElfi Kraka
Dec 19, 2020·Physical Chemistry Chemical Physics : PCCP·Markus BurschStefan Grimme
Jan 5, 2021·Journal of Computer-aided Molecular Design·Mehtap IşıkJohn D Chodera
Mar 11, 2021·The Journal of Physical Chemistry. a·Stefan GrimmeMarcel Stahn
Jun 5, 2021·The Journal of Physical Chemistry. a·Enric Petrus, Carles Bo
Jun 15, 2021·Journal of Computer-aided Molecular Design·Judith WarnauJens Reinisch
Jun 19, 2021·The Journal of Physical Chemistry. a·Philipp Pracht, Stefan Grimme
Jun 26, 2021·Journal of Computer-aided Molecular Design·Teresa Danielle BergazinDavid L Mobley
Jul 13, 2021·Journal of Chemical Information and Modeling·Xiaolin PanChangge Ji
May 2, 2020·Journal of Chemical Information and Modeling·Peter HuntMatthew Segall

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.