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Search · four archives
29 papers · ranked by Valyu relevance
Muhammad Waseem Sarwar, Adeel Riaz, Syed Muhammad Raihan Dilshad, Ahmed Al-Qahtani + 2 more
'Ahmed Al-Qahtani' 'Muhammad Shah Nawaz-Ul-Rehman' 'Muhammad Mubin'] Background Due to dengue virus disease, half of the world population is at severe health risk. Viral encoded NS2B-NS3 protease complex causes cleavage in the nonstructural region of the viral polyprotein. The cleavage is essentially required for fully…
Benson M Spowage, Craig L Bruce, Jonathan D Hirst
Background The topological maximum cross correlation (TMACC) descriptors are alignment-independent 2D descriptors for the derivation of QSARs. TMACC descriptors are generated using atomic properties determined by molecular topology. Previous validation (J Chem Inf Model 2007, 47: 626-634) of the TMACC descriptor…
Marcelo Tavares de Oliveira, Edson Katekawa
Quantitative Structure-Activity Relationship (QSAR) has proved an invaluable tool in medicinal chemistry. Data availability at unprecedented levels through various databases have collaborated to a resurgence in the interest for QSAR. In this context, rapid generation of quality predictive models is highly desirable for…
Rattanawan Tangporncharoen, Chuleeporn Phanus-Umporn, Supaluk Prachayasittikul, Chanin Nantasenamat + 2 more
Osteoanabolic agents, or drugs that promote bone formation, have gained considerable attention for osteoporosis management due to their curative and preventive potentials. Sphingosine-1-phosphate receptor 2 (S1PR2) is an attractive drug target, in which its activation leads to osteogenesis-promoting effect.…
Hezha O. Rasul, Dlzar D. Ghafour, Bakhtyar K. Aziz, Bryar A. Hassan + 2 more
'Tarik A. Rashid' 'Arif Kıvrak'] The drug development process is a critical challenge in the pharmaceutical industry due to its timeconsuming nature and the need to discover new drug potentials to address various ailments. The initial step in drug development, drug target identification, often consumes considerable…
Daniel T. Chang
Probabilistic generative deep learning for molecular design involves the discovery and design of new molecules and analysis of their structure, properties and activities by probabilistic generative models using the deep learning approach. It leverages the existing huge databases and publications of experimental…
José J. Naveja, Martin Vogt, Marta Erminia Alberto
Analogue series play a key role in drug discovery. They arise naturally in lead optimization efforts where analogues are explored based on one or a few core structures. However, it is much harder to accurately identify and extract pairs or series of analogue molecules in large compound databases with no predefined core…
Maria Yousuf, Nimra Naveed Shaikh, Zaheer Ul-Haq, M. Iqbal Choudhary + 1 more
'Y-h. Taguchi'] Identification of hotspot drug-receptor interactions through in-silico prediction methods (Pharmacophore mapping, virtual screening, 3DQSAR, etc), is considered as a key approach in drug designing and development process. In the current design study, advanced in-silico based computational techniques…
Kim, Hajung, Jueon Park, Choe + 5 more
Quantitative structure–activity relationship assumes a smooth relationship between molecular structure and biological activity. However, activity cliffs defined as pairs of structurally similar compounds with large potency differences break this continuity. Recent benchmarks targeting activity cliffs have revealed that…
Markus Dablander, Thierry Hanser, Renaud Lambiotte, Garrett M. Morris
'Garrett M. Morris'] Introduction and Methodology: Pairs of similar compounds that only differ by a small structural modification but exhibit a large difference in their binding affinity for a given target are known as activity cliffs (ACs). It has been hypothesised that QSAR models struggle to predict ACs and that ACs…
Alaa M. Elgohary, Abdo A. Elfiky, Florbela Pereira, Tarek Mohamed Abd El-Aziz + 3 more
Over a span of two years ago, since the emergence of the first case of the novel coronavirus (SARS-CoV-2) in China, the pandemic has crossed borders causing serious health emergencies, immense economic crisis and impacting the daily life worldwide. Despite the discovery of numerous forms of precautionary vaccines along…
Dagmar Stumpfe, Antonio de la Vega de León, Dilyana Dimova, Jürgen Bajorath
'Jürgen Bajorath'] We present a follow up contribution to further complement a previous commentary on the activity cliff concept and recent advances in activity cliff research. Activity cliffs have originally been defined as pairs of structurally similar compounds that display a large difference in potency against a…
Md. Aktar Hossain, Saima Sultana
In silico analysis is a powerful technique to identify better therapeutic interventions. Molecular docking is widely used to screen ligands through analysing binding affinities for target receptors. In this study we screened ligands for two proteins which are potential drug targets: deoxyuridine triphosphate…
Authors not listed
Staphylococcus aureus is a bacterium classified among the ESKAPE pathogens, which are anticipated to pose a significant global health emergency in the coming decades. The FabI enzyme, present in both Gram-positive and Gram-negative bacteria, is a key enzyme involved in fatty acid synthesis II (FAS-II). In this study…
Ioannis G. Riziotis, António J. M. Ribeiro, Neera Borkakoti, Janet M. Thornton
Conformational variation in catalytic residues can be captured as alternative snapshots in enzyme crystal structures. Addressing the question of whether active site flexibility is an intrinsic and essential property of enzymes for catalysis, we present a comprehensive study on the 3D variation of active sites of 925…
Edgar López-López, Oscar Robles, Fabien Plisson, José L. Medina-Franco
Peptides are a re-emerged strategy to fight a plethora of diseases and their utility has been expanded to new areas. Now sequence-based peptide design opens up new possibilities to develop peptidic molecular entities. However, its methodological limitations (e.g., its inefficiency in designing large peptides and that…
Huabin Hu, Jürgen Bajorath
Aim: Extending the public knowledge base of activity cliffs (ACs) with new categories of ACs having special structural characteristics. Methodology: Dual-site ACs, isomer ACs and ACs with privileged substructures are described and their systematic identification is detailed. Exemplary results & data: More than 7400 new…
Sharad Sarak, Hong Yang, Colin T. Pierce, Panhavuth Tan + 6 more
Active-site redesign frequently yields modest improvements because residues controlling physical steps like substrate binding and product release lie outside the active site. Efficient catalysis requires a cooperative catalytic network of residues that support both the chemical and physical steps of catalysis. Using…
Charles W.E. Tomlinson, Stefano Elli, Morgan Batiste-Simms, Zongjia Chen + 9 more
The enzymatic removal of sulfate groups regulates processes ranging from steroid metabolism to carbohydrate degradation. Most sulfatases belong to the S1 family, whose members use a co-translationally installed formylglycine residue to hydrolyse sulfate esters. Arylsulfamates are potent covalent inhibitors of aryl and…
Vladimir Potemkin, Maria Grishina, Sandro Azaele, Samir Simon Suweis
New approaches to assessing the “enzyme-ligand” complementarity, taking into account hydrogens, have been proposed. The approaches are based on the calculation of three-dimensional maps of the electron density of the receptor-ligand complexes. The action of complementarity factors, first proposed in this article, has…
Joseph Bemister-Buffington, Alex J. Wolf, Sebastian Raschka, Leslie A. Kuhn
We show that machine learning can pinpoint features distinguishing inactive from active states in proteins, in particular identifying key ligand binding site flexibility transitions in GPCRs that are triggered by biologically active ligands. Our analysis was performed on the helical segments and loops in 18 inactive…
Authors not listed
Fragment based drug design (FBDD) is like a chess game in that a good or a bad move can dramatically influence the outcome. At the start of the design process, it is important to identify the key binding site residues (hotspots) that can have a substantial impact on ligand efficiency (LE) and binding. Here, we…
Authors not listed
Macrocycles are emerging as a prominent modality in drug discovery, including for conventionally druggable targets for which simpler, acyclic ligands are readily discoverable. Given the additional synthetic challenges associated with macrocyclic chemotypes, we address what benefits macrocycles provided for these highly…
Ioannis G. Riziotis, Janet M. Thornton
Structural templates are 3D signatures representing protein functional sites, such as ligand binding cavities, metal coordination motifs or catalytic sites. Here we explore methods to generate template libraries and algorithms to query structures for conserved 3D motifs. Applications of templates are discussed, as well…
Chris Zhang, Mary Pitman, Anjali Dixit, Sumudu Leelananda + 7 more
DNA-encoded libraries (DELs) provide the means to make and screen millions of diverse compounds against a target of interest in a single experiment. However, despite producing large volumes of binding data at a relatively low cost, the DEL selection process is susceptible to noise, necessitating computational follow-up…
Jingwei Zuo, Hakim Hacid
Human Activity Recognition (HAR) has been studied for decades, from data collection, learning models, to post-processing and result interpretations. However, the inherent hierarchy in the activities remains relatively under-explored, despite its significant impact on model performance and interpretation. In this paper…
Avishek Ghosh, Arnab Ghosh, Arkabandhu Chowdhury, Jubin Hazra
— The present work provides a new approach to evolve ligand structures which represent possible drug to be docked to the active site of the target protein. The structure is represented as a tree where each non-empty node represents a functional group. It is assumed that the active site configuration of the target…
Jiming Chen, Diwakar Shukla
The strigolactone signaling pathway in plants is unconventional among plant hormone signaling pathways in that the receptor also acts as an enzyme that hydrolyzes the strigolactone substrate. While the canonical view of strigolactone hydrolysis is that it occurs via a nucleophilic attack on the butenolide ring of…
Jiming Chen, David C. Nelson, Diwakar Shukla
Parastic weeds such as Striga have led to significant losses in agricultural productivity worldwide. These weeds use the plant hormone strigolactone as a germination stimulant. Strigolactone signaling involves substrate binding and hydrolysis followed by a large conformational change of the receptor to a “closed” or…