Understanding the impact of binding free energy and kinetics calculations in modern drug discovery

VA Adediwura, K Koirala, HN Do, J Wang… - Expert Opinion on Drug …, 2024‏ - Taylor & Francis
Introduction For rational drug design, it is crucial to understand the receptor-drug binding
processes and mechanisms. A new era for the use of computer simulations in predicting …

Fragment-to-lead medicinal chemistry publications in 2021

L Walsh, DA Erlanson, IJP de Esch… - Journal of medicinal …, 2023‏ - ACS Publications
This Perspective is the seventh in an annual series that summarizes successful Fragment-to-
Lead (F2L) case studies published in a given year. A tabulated summary of relevant articles …

Brief report: Gender identity differences in autistic adults: Associations with perceptual and socio-cognitive profiles

RJ Walsh, L Krabbendam, J Dewinter… - Journal of autism and …, 2018‏ - Springer
Prior research has shown an elevation in autism traits and diagnoses in individuals seen for
gender related consultation and in participants self-identifying as transgender. To …

Evaluating the use of absolute binding free energy in the fragment optimisation process

I Alibay, A Magarkar, D Seeliger… - Communications Chemistry, 2022‏ - nature.com
Key to the fragment optimisation process within drug design is the need to accurately
capture the changes in affinity that are associated with a given set of chemical modifications …

Alchemical free energy calculations on membrane-associated proteins

M Papadourakis, H Sinenka, P Matricon… - Journal of Chemical …, 2023‏ - ACS Publications
Membrane proteins have diverse functions within cells and are well-established drug
targets. The advances in membrane protein structural biology have revealed drug and lipid …

Design of Drug Efficacy Guided by Free Energy Simulations of the β2‐Adrenoceptor

N Panel, DD Vo, NA Kahlous, H Hübner… - Angewandte Chemie …, 2023‏ - Wiley Online Library
G‐protein‐coupled receptors (GPCRs) play important roles in physiological processes and
are modulated by drugs that either activate or block signaling. Rational design of the …

Hit-to-Lead Optimization of Heterocyclic Carbonyloxycarboximidamides as Selective Antagonists at Human Adenosine A3 Receptor

X Huang, A Chorianopoulou, P Kalkounou… - Journal of Medicinal …, 2024‏ - ACS Publications
Antagonism of the human adenosine A3 receptor (hA3R) has potential therapeutic
application. Alchemical relative binding free energy calculations of K18 and K32 suggested …

Dual A1/A3 Adenosine Receptor Antagonists: Binding Kinetics and Structure− Activity Relationship Studies Using Mutagenesis and Alchemical Binding Free Energy …

M Stampelou, A Suchankova, E Tzortzini… - Journal of Medicinal …, 2022‏ - ACS Publications
Drugs targeting adenosine receptors (AR) can provide treatment for diseases. We report the
identification of 7-(phenylamino)-pyrazolo [3, 4-c] pyridines L2–L10, A15, and A17 as low …

Computational Workflow for Refining AlphaFold Models in Drug Design Using Kinetic and Thermodynamic Binding Calculations: A Case Study for the Unresolved …

M Stampelou, G Ladds… - The Journal of Physical …, 2024‏ - ACS Publications
A structure-based drug design pipeline that considers both thermodynamic and kinetic
binding data of ligands against a receptor will enable the computational design of improved …

Recent advances in structure, function, and pharmacology of class A lipid GPCRs: opportunities and challenges for drug discovery

RNV Krishna Deepak, RK Verma, YD Hartono… - Pharmaceuticals, 2021‏ - mdpi.com
Great progress has been made over the past decade in understanding the structural,
functional, and pharmacological diversity of lipid GPCRs. From the first determination of the …