Binding affinities
View article: The biochemical basis of microRNA targeting efficacy
The biochemical basis of microRNA targeting efficacy Open
Biochemical prediction of miRNA targeting MicroRNAs (miRNAs) regulate most human messenger RNAs and play essential roles in diverse developmental and physiological processes. Correctly predicting the function of each miRNA requires a bette…
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DeepDTA: deep drug–target binding affinity prediction Open
Motivation The identification of novel drug–target (DT) interactions is a substantial part of the drug discovery process. Most of the computational methods that have been proposed to predict DT interactions have focused on binary classific…
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<i>K</i><sub>DEEP</sub>: Protein–Ligand Absolute Binding Affinity Prediction via 3D-Convolutional Neural Networks Open
Accurately predicting protein-ligand binding affinities is an important problem in computational chemistry since it can substantially accelerate drug discovery for virtual screening and lead optimization. We propose here a fast machine-lea…
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Relative Binding Free Energy Calculations in Drug Discovery: Recent Advances and Practical Considerations Open
Accurate in silico prediction of protein-ligand binding affinities has been a primary objective of structure-based drug design for decades due to the putative value it would bring to the drug discovery process. However, computational metho…
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SARS-CoV-2 Omicron variant: Antibody evasion and cryo-EM structure of spike protein–ACE2 complex Open
The newly reported Omicron variant is poised to replace Delta as the most prevalent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant across the world. Cryo–electron microscopy (cryo-EM) structural analysis of the Omicro…
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Design of protein-binding proteins from the target structure alone Open
The design of proteins that bind to a specific site on the surface of a target protein using no information other than the three-dimensional structure of the target remains a challenge 1–5 . Here we describe a general solution to this prob…
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How to measure and evaluate binding affinities Open
Quantitative measurements of biomolecule associations are central to biological understanding and are needed to build and test predictive and mechanistic models. Given the advances in high-throughput technologies and the projected increase…
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Predicting Binding Free Energies: Frontiers and Benchmarks Open
Binding free energy calculations based on molecular simulations provide predicted affinities for biomolecular complexes. These calculations begin with a detailed description of a system, including its chemical composition and the interacti…
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Ligand-Binding Affinity Estimates Supported by Quantum-Mechanical Methods Open
One of the largest challenges of computational chemistry is calculation of accurate free energies for the binding of a small molecule to a biological macromolecule, which has immense implications in drug development. It is well-known that …
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Large scale relative protein ligand binding affinities using non-equilibrium alchemy Open
Relative ligand binding affinity calculations based on molecular dynamics (MD) simulations and non-physical (alchemical) thermodynamic cycles have shown great promise for structure-based drug design.
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Cyclic peptide drugs approved in the last two decades (2001–2021) Open
In this mini-review, we summarized the chemical structure, mechanism of action, and metabolism of cyclic peptide drugs approved in the last two decades. We also examined factors important for the development and utilization in clinical sit…
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Docking Screens for Novel Ligands Conferring New Biology Open
It is now plausible to dock libraries of 10 million molecules against targets over several days or weeks. When the molecules screened are commercially available, they may be rapidly tested to find new leads. Although docking retains import…
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Intrinsically disordered RGG/RG domains mediate degenerate specificity in RNA binding Open
RGG/RG domains are the second most common RNA binding domain in the human genome, yet their RNA-binding properties remain poorly understood. Here, we report a detailed analysis of the RNA binding characteristics of intrinsically disordered…
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Methods for Improving Aptamer Binding Affinity Open
Aptamers are single stranded oligonucleotides that bind a wide range of biological targets. Although aptamers can be isolated from pools of random sequence oligonucleotides using affinity-based selection, aptamers with high affinities are …
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Low-Affinity Binding Sites and the Transcription Factor Specificity Paradox in Eukaryotes Open
Eukaryotic transcription factors (TFs) from the same structural family tend to bind similar DNA sequences, despite the ability of these TFs to execute distinct functions in vivo. The cell partly resolves this specificity paradox through co…
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Assessment of Binding Affinity via Alchemical Free-Energy Calculations Open
Free-energy calculations have seen increased usage in structure-based drug design. Despite the rising interest, automation of the complex calculations and subsequent analysis of their results are still hampered by the restricted choice of …
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Predictions of Ligand Selectivity from Absolute Binding Free Energy Calculations Open
Binding selectivity is a requirement for the development of a safe drug, and it is a critical property for chemical probes used in preclinical target validation. Engineering selectivity adds considerable complexity to the rational design o…
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Computational prediction of protein–protein binding affinities Open
Protein–protein interactions form central elements of almost all cellular processes. Knowledge of the structure of protein–protein complexes but also of the binding affinity is of major importance to understand the biological function of p…
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On the Frustration to Predict Binding Affinities from Protein–Ligand Structures with Deep Neural Networks Open
Accurate prediction of binding affinities from protein-ligand atomic coordinates remains a major challenge in early stages of drug discovery. Using modular message passing graph neural networks describing both the ligand and the protein in…
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Application of MM-PBSA Methods in Virtual Screening Open
Computer-aided drug design techniques are today largely applied in medicinal chemistry. In particular, receptor-based virtual screening (VS) studies, in which molecular docking represents the gold standard in silico approach, constitute a …
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Systematically benchmarking peptide-MHC binding predictors: From synthetic to naturally processed epitopes Open
A number of machine learning-based predictors have been developed for identifying immunogenic T-cell epitopes based on major histocompatibility complex (MHC) class I and II binding affinities. Rationally selecting the most appropriate tool…
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The SARS-CoV-2 Exerts a Distinctive Strategy for Interacting with the ACE2 Human Receptor Open
The COVID-19 disease has plagued over 200 countries with over three million cases and has resulted in over 200,000 deaths within 3 months. To gain insight into the high infection rate of the SARS-CoV-2 virus, we compare the interaction bet…
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Is It Reliable to Use Common Molecular Docking Methods for Comparing the Binding Affinities of Enantiomer Pairs for Their Protein Target? Open
Molecular docking is a computational chemistry method which has become essential for the rational drug design process. In this context, it has had great impact as a successful tool for the study of ligand–receptor interaction modes, and fo…
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Rapid, accurate, precise and reproducible ligand–protein binding free energy prediction Open
A central quantity of interest in molecular biology and medicine is the free energy of binding of a molecule to a target biomacromolecule. Until recently, the accurate prediction of binding affinity had been widely regarded as out of reach…
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Statistical Analysis on the Performance of Molecular Mechanics Poisson–Boltzmann Surface Area versus Absolute Binding Free Energy Calculations: Bromodomains as a Case Study Open
Binding free energy calculations that make use of alchemical pathways are becoming increasingly feasible thanks to advances in hardware and algorithms. Although relative binding free energy (RBFE) calculations are starting to find widespre…
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Comparison Study of Computational Prediction Tools for Drug-Target Binding Affinities Open
The drug development is generally arduous, costly, and success rates are low. Thus, the identification of drug-target interactions (DTIs) has become a crucial step in early stages of drug discovery. Consequently, developing computational a…
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Scoring Functions for Protein-Ligand Binding Affinity Prediction Using Structure-based Deep Learning: A Review Open
The rapid and accurate in silico prediction of protein-ligand binding free energies or binding affinities has the potential to transform drug discovery. In recent years, there has been a rapid growth of interest in deep learning methods fo…
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STCRDab: the structural T-cell receptor database Open
The Structural T-cell Receptor Database (STCRDab; http://opig.stats.ox.ac.uk/webapps/stcrdab) is an online resource that automatically collects and curates TCR structural data from the Protein Data Bank. For each entry, the database provid…
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Recent Developments in Free Energy Calculations for Drug Discovery Open
The grand challenge in structure-based drug design is achieving accurate prediction of binding free energies. Molecular dynamics (MD) simulations enable modeling of conformational changes critical to the binding process, leading to calcula…
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CSM-lig: a web server for assessing and comparing protein–small molecule affinities Open
Determining the affinity of a ligand for a given protein is a crucial component of drug development and understanding their biological effects. Predicting binding affinities is a challenging and difficult task, and despite being regarded a…