Exploring biomolecular energy landscapes

Jerelle A. Joseph, Konstantin Röder, Debayan Chakraborty, Rosemary G. Mantell and David J. Wales

Chem. Commun., 2017, 53, 6974
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Inducing high activity of a thermophilic enzyme at ambient temperatures by directed evolution

Guangyue Li, Miguel A. Maria-Solano, Adrian Romero-Rivera, Sílvia Osuna and Manfred T. Reetz

Chem. Commun., 2017, 53, 9454
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Protein conformational ensembles in function: roles and mechanisms

Ruth Nussinov, Yonglan Liu, Wengang Zhang and Hyunbum Jang

RSC Chem. Biol., 2023, 4, 850
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Allosteric Modalities for Membrane-Bound Receptors: Insights from Drug Hunting for Brain Diseases

Quinn Coughlin, Allen T. Hopper, Maria-Jesus Blanco, Vijaya Tirunagaru, Albert J. Robichaud and Dario Doller

J. Med. Chem., 2019, 62, 5979
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Advancements and Challenges in Computational Biology

Ruth Nussinov

PLoS Comput Biol, 2015, 11, e1004053
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Innovative Strategies in X-ray Crystallography for Exploring Structural Dynamics and Reaction Mechanisms in Metabolic Disorders

Alice Grieco, Isabel Quereda-Moraleda and Jose Manuel Martin-Garcia

JPM, 2024, 14, 909
DOI: 10.3390/jpm14090909

Allostery in Disease: Anticancer Drugs, Pockets, and the Tumor Heterogeneity Challenge

Ruth Nussinov, Bengi Ruken Yavuz and Hyunbum Jang

Journal of Molecular Biology, 2025, 169050
DOI: 10.1016/j.jmb.2025.169050

Protein Folding and Mechanisms of Proteostasis

José Díaz-Villanueva, Raúl Díaz-Molina and Victor García-González

IJMS, 2015, 16, 17193
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Energy Landscapes in Chemical Reactions and Transport

Karl‐Michael Weitzel

ChemPhysChem, 2025, 26
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Ras Conformational Ensembles, Allostery, and Signaling

Shaoyong Lu, Hyunbum Jang, Serena Muratcioglu, Attila Gursoy, Ozlem Keskin, Ruth Nussinov and Jian Zhang

Chem. Rev., 2016, 116, 6607
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Evolutionary drivers of thermoadaptation in enzyme catalysis

Vy Nguyen, Christopher Wilson, Marc Hoemberger, John B. Stiller, Roman V. Agafonov, Steffen Kutter, Justin English, Douglas L. Theobald and Dorothee Kern

Science, 2017, 355, 289
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Bivalent molecular mimicry by ADP protects metal redox state and promotes coenzyme B 12 repair

Harsha Gouda, Romila Mascarenhas, Markus Ruetz, Madeline Yaw and Ruma Banerjee

Proc. Natl. Acad. Sci. U.S.A., 2023, 120
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Balancing multiple objectives in conformation sampling to control decoy diversity in template-free protein structure prediction

Ahmed Bin Zaman and Amarda Shehu

BMC Bioinformatics, 2019, 20
DOI: 10.1186/s12859-019-2794-5

Weight average approaches for predicting dynamical properties of biomolecules

Kiyoshi Yagi, Suyong Re, Takaharu Mori and Yuji Sugita

Current Opinion in Structural Biology, 2022, 72, 88
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Examining a Thermodynamic Order Parameter of Protein Folding

Song-Ho Chong and Sihyun Ham

Sci Rep, 2018, 8
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Phosphorylation-induced changes in the energetic frustration in human Tank binding kinase 1

Shahrukh Husain, Vijay Kumar and Md. Imtaiyaz Hassan

Journal of Theoretical Biology, 2018, 449, 14
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Protein Ensembles: How Does Nature Harness Thermodynamic Fluctuations for Life? The Diverse Functional Roles of Conformational Ensembles in the Cell

Guanghong Wei, Wenhui Xi, Ruth Nussinov and Buyong Ma

Chem. Rev., 2016, 116, 6516
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Binding Modalities and Phase-Specific Regulation of Cyclin/Cyclin-Dependent Kinase Complexes in the Cell Cycle

Michael T. Bergman, Wengang Zhang, Yonglan Liu, Hyunbum Jang and Ruth Nussinov

J. Phys. Chem. B, 2024, 128, 9315
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Generative deep learning for macromolecular structure and dynamics

Pourya Hoseini, Liang Zhao and Amarda Shehu

Current Opinion in Structural Biology, 2021, 67, 170
DOI: 10.1016/j.sbi.2020.11.012

Tandem Domains with Tuned Interactions Are a Powerful Biological Design Principle

Ruth Nussinov and Chung-Jung Tsai

PLoS Biol, 2015, 13, e1002306
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Higher-Order DNA Secondary Structures and Their Transformations: The Hidden Complexities of Tetrad and Quadruplex DNA Structures, Complexes, and Modulatory Interactions Induced by Strand Invasion Events

Jens Völker, Vera Gindikin and Kenneth J. Breslauer

Biomolecules, 2024, 14, 1532
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Precision medicine review: rare driver mutations and their biophysical classification

Ruth Nussinov, Hyunbum Jang, Chung-Jung Tsai and Feixiong Cheng

Biophys Rev, 2019, 11, 5
DOI: 10.1007/s12551-018-0496-2

Limits in accuracy and a strategy of RNA structure prediction using experimental information

Jian Wang, Benfeard Williams, Venkata R Chirasani, Andrey Krokhotin, Rajeshree Das and Nikolay V Dokholyan

Nucleic Acids Research, 2019, 47, 5563
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Protein ensembles link genotype to phenotype

Ruth Nussinov, Chung-Jung Tsai, Hyunbum Jang and Ignacio Bravo

PLoS Comput Biol, 2019, 15, e1006648
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Allostery: Allosteric Cancer Drivers and Innovative Allosteric Drugs

Ruth Nussinov, Mingzhen Zhang, Ryan Maloney, Yonglan Liu, Chung-Jung Tsai and Hyunbum Jang

Journal of Molecular Biology, 2022, 434, 167569
DOI: 10.1016/j.jmb.2022.167569

AlphaFold, Artificial Intelligence (AI), and Allostery

Ruth Nussinov, Mingzhen Zhang, Yonglan Liu and Hyunbum Jang

J. Phys. Chem. B, 2022, 126, 6372
DOI: 10.1021/acs.jpcb.2c04346

Elucidating the Role of Wildtype and Variant FGFR2 Structural Dynamics in (Dys)Function and Disorder

Yiyang Lian, Dale Bodian and Amarda Shehu

IJMS, 2024, 25, 4523
DOI: 10.3390/ijms25084523

The structural basis for cancer treatment decisions

Ruth Nussinov, Hyunbum Jang and Chung-Jung Tsai

Oncotarget, 2014, 5, 7285
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Allosteric changes in the conformational landscape of Src kinase upon substrate binding

Song-Ho Chong, Hiraku Oshima and Yuji Sugita

Journal of Molecular Biology, 2024, 168871
DOI: 10.1016/j.jmb.2024.168871

Attenuating dependence on structural data in computing protein energy landscapes

David Morris, Tatiana Maximova, Erion Plaku and Amarda Shehu

BMC Bioinformatics, 2019, 20
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An Information-Theory-Based Approach for Optimal Model Reduction of Biomolecules

Marco Giulini, Roberto Menichetti, M. Scott Shell and Raffaello Potestio

J. Chem. Theory Comput., 2020, 16, 6795
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From molecular energy landscapes to equilibrium dynamics via landscape analysis and markov state models

Kazi Lutful Kabir, Nasrin Akhter and Amarda Shehu

J. Bioinform. Comput. Biol., 2019, 17, 1940014
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From Extraction of Local Structures of Protein Energy Landscapes to Improved Decoy Selection in Template-Free Protein Structure Prediction

Nasrin Akhter and Amarda Shehu

Molecules, 2018, 23, 216
DOI: 10.3390/molecules23010216

How residence time works in allosteric drugs

Ruth Nussinov and Hyunbum Jang

Current Opinion in Structural Biology, 2025, 94, 103149
DOI: 10.1016/j.sbi.2025.103149

From Pathogens to Cancer: Are Cancer Cells Evolved Mitochondrial Super Cells?

Mario Balzanelli, Pietro Distratis, Rita Lazzaro, Van Pham, Raffaele Del Prete, Adriana Mosca, Francesco Inchingolo, Sergey Aityan, Luigi Santacroce, Kieu Nguyen and Ciro Gargiulo Isacco

Diagnostics, 2023, 13, 813
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Unsupervised and Supervised Learning over the Energy Landscape for Protein Decoy Selection

Nasrin Akhter, Gopinath Chennupati, Kazi Lutful Kabir, Hristo Djidjev and Amarda Shehu

Biomolecules, 2019, 9, 607
DOI: 10.3390/biom9100607

Allostery in Disease: From Mutations, Mechanisms, and Signalling Partners to Diagnostic and Drug Therapies

Igor N. Berezovsky and Ruth Nussinov

Journal of Molecular Biology, 2025, 169407
DOI: 10.1016/j.jmb.2025.169407

Open Structural Data in Precision Medicine

Ruth Nussinov, Hyunbum Jang, Guy Nir, Chung-Jung Tsai and Feixiong Cheng

Annu. Rev. Biomed. Data Sci., 2022, 5, 95
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TRAF3 signaling: Competitive binding and evolvability of adaptive viral molecular mimicry

Emine Guven-Maiorov, Ozlem Keskin, Attila Gursoy, Carter VanWaes, Zhong Chen, Chung-Jung Tsai and Ruth Nussinov

Biochimica et Biophysica Acta (BBA) - General Subjects, 2016, 1860, 2646
DOI: 10.1016/j.bbagen.2016.05.021

Modeling Binding with Large Conformational Changes: Key Points in Ensemble-Docking Approaches

Stefano Motta and Laura Bonati

J. Chem. Inf. Model., 2017, 57, 1563
DOI: 10.1021/acs.jcim.7b00125

Are Parallel Proliferation Pathways Redundant?

Ruth Nussinov, Chung-Jung Tsai and Hyunbum Jang

Trends in Biochemical Sciences, 2020, 45, 554
DOI: 10.1016/j.tibs.2020.03.013

AlphaFold, allosteric, and orthosteric drug discovery: Ways forward

Ruth Nussinov, Mingzhen Zhang, Yonglan Liu and Hyunbum Jang

Drug Discovery Today, 2023, 28, 103551
DOI: 10.1016/j.drudis.2023.103551

An Energy Landscape Treatment of Decoy Selection in Template-Free Protein Structure Prediction

Nasrin Akhter, Wanli Qiao and Amarda Shehu

Computation, 2018, 6, 39
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Conformational Ensemble of TteAdoCbl Riboswitch Provides Stable Structural Elements for Conformation Selection and Population Shift in Cobalamin Recognition

Buyong Ma, Ganggang Bai, Ruth Nussinov, Jienyu Ding and Yun-Xing Wang

J. Phys. Chem. B, 2021, 125, 2589
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Perspectives on the landscape and flux theory for describing emergent behaviors of the biological systems

Jin Wang

J Biol Phys, 2022, 48, 1
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Simplification of complexity in protein molecular systems by grouping amino acids: a view from physics

Jun Wang and Wei Wang

Advances in Physics: X, 2016, 1, 444
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From mutations to mechanisms and dysfunction via computation and mining of protein energy landscapes

Wanli Qiao, Nasrin Akhter, Xiaowen Fang, Tatiana Maximova, Erion Plaku and Amarda Shehu

BMC Genomics, 2018, 19
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Does Ras Activate Raf and PI3K Allosterically?

Ruth Nussinov, Chung-Jung Tsai and Hyunbum Jang

Front. Oncol., 2019, 9
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Allostery, and how to define and measure signal transduction

Ruth Nussinov, Chung-Jung Tsai and Hyunbum Jang

Biophysical Chemistry, 2022, 283, 106766
DOI: 10.1016/j.bpc.2022.106766

Conformational interdomain flexibility in a bacterial α-isopropylmalate synthase is necessary for leucine biosynthesis

Yu Bai, Wanting Jiao, Jan Vörster and Emily J. Parker

Journal of Biological Chemistry, 2023, 299, 102789
DOI: 10.1016/j.jbc.2022.102789

PDEδ Binding to Ras Isoforms Provides a Route to Proper Membrane Localization

Serena Muratcioglu, Hyunbum Jang, Attila Gursoy, Ozlem Keskin and Ruth Nussinov

J. Phys. Chem. B, 2017, 121, 5917
DOI: 10.1021/acs.jpcb.7b03035

Capturing dynamic conformational shifts in protein–ligand recognition using integrative structural biology in solution

Marcellus Ubbink, Anastassis Perrakis, Hyun-Seo Kang and Michael Sattler

Emerging Topics in Life Sciences, 2018, 2, 107
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Introduction to Protein Ensembles and Allostery

Ruth Nussinov

Chem. Rev., 2016, 116, 6263
DOI: 10.1021/acs.chemrev.6b00283

First-passage times in complex energy landscapes: a case study with nonmuscle myosin II assembly

Rick Bebon and Ulrich S Schwarz

New J. Phys., 2022, 24, 063034
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Intrinsic protein disorder in oncogenic KRAS signaling

Ruth Nussinov, Hyunbum Jang, Chung-Jung Tsai, Tsung-Jen Liao, Shuai Li, David Fushman and Jian Zhang

Cell. Mol. Life Sci., 2017, 74, 3245
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Discovery of hidden allosteric sites as novel targets for allosteric drug design

Shaoyong Lu, Mingfei Ji, Duan Ni and Jian Zhang

Drug Discovery Today, 2018, 23, 359
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How do mutations and allosteric inhibitors modulate caspase-7 activity? A molecular dynamics study

Elif Naz Bingöl, Onur Serçinoğlu and Pemra Ozbek

Journal of Biomolecular Structure and Dynamics, 2019, 37, 3456
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Optimal Coarse-Grained Site Selection in Elastic Network Models of Biomolecules

Patrick Diggins, Changjiang Liu, Markus Deserno and Raffaello Potestio

J. Chem. Theory Comput., 2019, 15, 648
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Sample-Based Models of Protein Energy Landscapes and Slow Structural Rearrangements

Tatiana Maximova, Zijing Zhang, Daniel B. Carr, Erion Plaku and Amarda Shehu

Journal of Computational Biology, 2018, 25, 33
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Probing biological mechanisms with chemical tools

Congbao Kang and Thomas H. Keller

Pharmacological Research, 2020, 153, 104656
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Inhibition of Nonfunctional Ras

Ruth Nussinov, Hyunbum Jang, Attila Gursoy, Ozlem Keskin and Vadim Gaponenko

Cell Chemical Biology, 2021, 28, 121
DOI: 10.1016/j.chembiol.2020.12.012

Unravelling the complexity of signalling networks in cancer: A review of the increasing role for computational modelling

John Garland

Critical Reviews in Oncology/Hematology, 2017, 117, 73
DOI: 10.1016/j.critrevonc.2017.06.004

Autoinhibition in Ras effectors Raf, PI3Kα, and RASSF5: a comprehensive review underscoring the challenges in pharmacological intervention

Ruth Nussinov, Mingzhen Zhang, Chung-Jung Tsai, Tsung-Jen Liao, David Fushman and Hyunbum Jang

Biophys Rev, 2018, 10, 1263
DOI: 10.1007/s12551-018-0461-0

Explicit Characterization of the Free Energy Landscape of pKID–KIX Coupled Folding and Binding

Song-Ho Chong, Haeri Im and Sihyun Ham

ACS Cent. Sci., 2019, 5, 1342
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Decoy selection for protein structure prediction via extreme gradient boosting and ranking

Nasrin Akhter, Gopinath Chennupati, Hristo Djidjev and Amarda Shehu

BMC Bioinformatics, 2020, 21
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Conformational footprints

Buyong Ma and Ruth Nussinov

Nat Chem Biol, 2016, 12, 890
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A perspective on bridging scales and design of models using low-dimensional manifolds and data-driven model inference

Jesper Tegnér, Hector Zenil, Narsis A. Kiani, Gordon Ball and David Gomez-Cabrero

Phil. Trans. R. Soc. A., 2016, 374, 20160144
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Structure‐Based Drug Discovery with Deep Learning**

R. Özçelik, D. van Tilborg, J. Jiménez‐Luna and F. Grisoni

ChemBioChem, 2023, 24
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Review: Precision medicine and driver mutations: Computational methods, functional assays and conformational principles for interpreting cancer drivers

Ruth Nussinov, Hyunbum Jang, Chung-Jung Tsai, Feixiong Cheng and Anna R R Panchenko

PLoS Comput Biol, 2019, 15, e1006658
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Drug resistance and tumor heterogeneity: cells and ensembles

Ruth Nussinov, Bengi Ruken Yavuz and Hyunbum Jang

Biophys Rev, 2025, 17, 759
DOI: 10.1007/s12551-025-01320-y

Large-Scale Conformational Changes and Protein Function: Breaking the in silico Barrier

Laura Orellana

Front. Mol. Biosci., 2019, 6
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Distributions of experimental protein structures on coarse-grained free energy landscapes

Kannan Sankar, Jie Liu, Yuan Wang and Robert L. Jernigan

The Journal of Chemical Physics, 2015, 143
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The disordered hypervariable region and the folded catalytic domain of oncogenic K-Ras4B partner in phospholipid binding

Avik Banerjee, Hyunbum Jang, Ruth Nussinov and Vadim Gaponenko

Current Opinion in Structural Biology, 2016, 36, 10
DOI: 10.1016/j.sbi.2015.11.010

Out-of-Equilibrium Biophysical Chemistry: The Case for Multidimensional, Integrated Single-Molecule Approaches

Narendar Kolimi, Ashok Pabbathi, Nabanita Saikia, Feng Ding, Hugo Sanabria and Joshua Alper

J. Phys. Chem. B, 2021, 125, 10404
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Golf-course and funnel energy landscapes: Protein folding concepts in martensites

N. Shankaraiah

Phys. Rev. E, 2017, 95
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Ligand Binding Thermodynamics in Drug Discovery: Still a Hot Tip?

Stefan Geschwindner, Johan Ulander and Patrik Johansson

J. Med. Chem., 2015, 58, 6321
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Principles and Overview of Sampling Methods for Modeling Macromolecular Structure and Dynamics

Tatiana Maximova, Ryan Moffatt, Buyong Ma, Ruth Nussinov, Amarda Shehu and Bert L. de Groot

PLoS Comput Biol, 2016, 12, e1004619
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Mechanism of activation and the rewired network: New drug design concepts

Ruth Nussinov, Mingzhen Zhang, Ryan Maloney, Chung‐Jung Tsai, Bengi Ruken Yavuz, Nurcan Tuncbag and Hyunbum Jang

Medicinal Research Reviews, 2022, 42, 770
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Autoinhibition can identify rare driver mutations and advise pharmacology

Ruth Nussinov, Chung‐Jung Tsai and Hyunbum Jang

The FASEB Journal, 2020, 34, 16
DOI: 10.1096/fj.201901341R