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p27$^{Kip1}$ (p27) is an intrinsically disordered protein (IDP) that folds upon binding to cyclin-dependent kinase (Cdk)$/$cyclin complexes (e.g., Cdk2$/$cyclin A), inhibiting their catalytic activity and causing cell cycle arrest. However,…

Proteins are only moderately stable. It has long been debated whether this narrow range of stabilities is solely a result of neutral drift towards lower stability or purifying selection against excess stability is also at work - for which…

Biomolecules · Quantitative Biology 2022-10-12 Bharat V. Adkar , Sanchari Bhattacharyya , Amy I. Gilson , Wenli Zhang , Eugene I. Shakhnovich

Binding kinetic parameters can be correlated with drug efficacy, which led to the development of various computational methods for predicting binding kinetic rates and gaining insight into protein-drug binding paths and mechanisms in recent…

Biomolecules · Quantitative Biology 2022-09-27 Farzin Sohraby , Ariane Nunes-Alves

How ATP binding initiates the docking process of kinesin's neck linker is a key question in understanding kinesin mechanism. It is believed that the formation of an extra turn structure by the first three amino acids of neck linker (LYS325,…

Biological Physics · Physics 2014-10-14 Yi-Zhao Geng , Qing Ji , Shu-Xia Liu , Shiwei Yan

The AlphaFold computer program predicted protein structures for the whole human genome, which has been considered as a remarkable breakthrough both in artificial intelligence (AI) application and structural biology. Despite the varying…

The intrinsic dynamics of most proteins are central to their function. Protein tyrosine kinases such as Abl1 undergo significant conformational changes that modulate their activity in response to different stimuli. These conformational…

Biological Physics · Physics 2025-08-12 Gabriel Monteiro da Silva , Kyle Lam , David C. Dalgarno , Brenda M. Rubenstein

Collapsin response mediator protein CRMP2 (gene: DPYSL2) is crucial for neuronal development. The homotetrameric CRMP2 complex is regulated via two mechanisms, first by phosphorylation at, and second by reduction and oxidation of the Cys504…

Biomolecules · Quantitative Biology 2017-03-30 Daniel Möller , Manuela Gellert , Walter Langel , Christopher Horst Lillig

In order to inquire the microscopic origin of observed multiple time scales in solvation dynamics we carry out several computer experiments. We perform atomistic molecular dynamics simulations on three protein-water systems namely,…

Soft Condensed Matter · Physics 2017-10-18 Sayantan Mondal , Saumyak Mukherjee , Biman Bagchi

The role of the rigidity of a peptide chain in its equilibrium dynamics is investigated within a realistic model with stringent microscopically derived coupling interaction potential and effective on-site potential. The coupling interaction…

Soft Condensed Matter · Physics 2007-06-25 A. E. Sitnitsky

In many organisms, cell division is driven by the constriction of a cytokinetic ring, which consists of actin filaments and crosslinking proteins. While it has long been believed that the constriction is driven by motor proteins, it has…

Biological Physics · Physics 2023-07-26 Alexander Cumberworth , Pieter Rein ten Wolde

The catalytic conversion ATP + AMP -> 2ADP by the enzyme adenylate kinase (ADK) involves the binding of one ATP molecule to the LID domain and one AMP molecule to the NMP domain. The latter is followed by a phosphate transfer, and then the…

Statistical Mechanics · Physics 2010-12-22 Bharat V. Adkar , Biman Jana , Biman Bagchi

The activities and interactions of proteins that govern the cellular response to a signal generate a multitude of protein phosphorylation states and heterogeneous protein complexes. Here, using a computational model that accounts for 307…

Molecular Networks · Quantitative Biology 2007-05-23 James R. Faeder , Michael L. Blinov , Byron Goldstein , William S. Hlavacek

Multivalent associative proteins with strong complementary interactions play a crucial role in phase separation of intracellular liquid condensates. We study the internal dynamics of such "bond-network" condensates comprised of two…

Soft Condensed Matter · Physics 2022-02-02 Pierre Ronceray , Yaojun Zhang , Xichong Liu , Ned S. Wingreen

About half of human cancers show normal TP53 gene and aberrant overexpression of Mdm2 and/or MdmX. This fact promotes a promising cancer therapeutic strategy which targeting the interactions between p53 and Mdm2/MdmX. For developing the…

Molecular Networks · Quantitative Biology 2017-01-25 Shuxia Liu , Yizhao Geng , Shiwei Yan

In the context of epigenetic transformations in cancer metastasis, a puzzling effect was recently discovered, in which the elimination (knock-out) of an activating regulatory element leads to increased (rather than decreased) activity of…

Molecular Networks · Quantitative Biology 2024-10-30 M. Ali Al-Radhawi , Krishna Manoj , Dhruv D. Jatkar , Alon Duvall , Domitilla Del Vecchio , Eduardo D. Sontag

We study the binding of plant hormone IAA on its receptor TIR1 introducing a novel computational method that we call tomographic docking and that accounts for interactions occurring along the depth of the binding pocket. Our results suggest…

Biomolecules · Quantitative Biology 2016-10-20 Veselina V. Uzunova , Mussa Quareshy , Charo I. del Genio , Richard M. Napier

Starting from the lead structure we have identified in our previous works, we are extending our insight understanding of its potential inhibitory effect against both EGFR and HER2 receptors. Herein and using extended molecular dynamic…

Biomolecules · Quantitative Biology 2013-05-30 Marawan Ahmed , Maiada M. Sadek , Khaled A. Abouzid , Feng Wang

Cyclic peptides offer inherent advantages in pharmaceuticals. For example, cyclic peptides are more resistant to enzymatic hydrolysis compared to linear peptides and usually exhibit excellent stability and affinity. Although deep generative…

Machine Learning · Computer Science 2025-05-28 Xiangxin Zhou , Mingyu Li , Yi Xiao , Jiahan Li , Dongyu Xue , Zaixiang Zheng , Jianzhu Ma , Quanquan Gu

The functionality of protein-protein complexes is closely tied to the strength of their interactions, making the evaluation of binding affinity a central focus in structural biology. However, the molecular determinants underlying binding…

We study the high-frequency micro-mechanical response of suspensions composed by cardiac and skeletal muscle myosin by optical trapping interferometry. We observe that in low ionic strength solutions upon the addition of magnesium adenosine…

Soft Condensed Matter · Physics 2024-10-15 Pablo Domínguez-García , Jose R. Pinto , Ana Akrap , Sylvia Jeney
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