Performance of CHARMM36m with modified water model in simulating intrinsically disordered proteins: a case study

Pineda, Laura I. Gil; Milko, Laurie N.; He, Yi

doi:10.1007/s41048-020-00107-w

Cited by 20 publications

(11 citation statements)

References 46 publications

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“…In particular, it is proving difficult to obtain a good balance between the properties of unstructured IDPs and the properties of small folded proteins using the same FF. 31,34,44,47,48 Our own attempts to improve FFs for molecular simulation started nearly 20 years ago, with the impetus arising naturally out of a desire to understand the effects of cosolvents on biomolecules. 49−52 Initially, we simply noted interesting observations using extant FFs.…”

Section: ■ Introductionmentioning

confidence: 99%

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Kirkwood–Buff-Derived Force Field for Peptides and Proteins: Philosophy and Development of KBFF20

Ploetz

Karunaweera

Bentenitis

et al. 2021

J. Chem. Theory Comput.

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A new classical nonpolarizable force field, KBFF20, for the simulation of peptides and proteins is presented. The force field relies heavily on the use of Kirkwood−Buff theory to provide a comparison of simulated and experimental Kirkwood−Buff integrals for solutes containing the functional groups common in proteins, thus ensuring intermolecular interactions that provide a good balance between the peptide−peptide, peptide−solvent, and solvent−solvent distributions observed in solution mixtures. In this way, it differs significantly from other biomolecular force fields. Further development and testing of the intermolecular potentials are presented here. Subsequently, rotational potentials for the ϕ/ψ and χ dihedral degrees of freedom are obtained by analysis of the Protein Data Bank, followed by small modifications to provide a reasonable balance between simulated and observed α and β percentages for small peptides. This, the first of two articles, describes in detail the philosophy and development behind KBFF20.

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Section: ■ Introductionmentioning

confidence: 99%

“…Nevertheless, problems still exist. In particular, it is proving difficult to obtain a good balance between the properties of unstructured IDPs and the properties of small folded proteins using the same FF. ,,,, …”

Section: Introductionmentioning

confidence: 99%

Kirkwood–Buff-Derived Force Field for Peptides and Proteins: Philosophy and Development of KBFF20

Ploetz

Karunaweera

Bentenitis

et al. 2021

J. Chem. Theory Comput.

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“… 76 While the recently developed a99SB-disp is optimally parameterized for both folded and disordered proteins with substantially improved accuracy, 76 the requirement of a four-point water model significantly increases computational costs; the force field is also reported to be too soluble for studying aggregations of some disordered proteins. 91 , 92 Other important IDP-specific AMBER force fields include ff99IDPs, 93 , 94 ff14IDPs, 94 , 95 and ff14IDPSFF 94 , 96 , 97 with the TIP3P water model, 87 which were optimized by incorporating different backbone torsion parameters from different amino-acid groups including certain disorder-promoting amino acids. Here, we propose and demonstrate the use of two protein force fields compatible with three-point CHARMM-modified TIP3P water, namely, CHARMM36m and CHARMM22*, in combination with our chosen sampling methods.…”

Section: Introductionmentioning

confidence: 99%

Modeling the Structure and Interactions of Intrinsically Disordered Peptides with Multiple Replica, Metadynamics-Based Sampling Methods and Force-Field Combinations

Casalini

Arosio

et al. 2022

J. Chem. Theory Comput.

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Intrinsically disordered proteins play a key role in many biological processes, including the formation of biomolecular condensates within cells. A detailed characterization of their configurational ensemble and structure–function paradigm is crucial for understanding their biological activity and for exploiting them as building blocks in material sciences. In this work, we incorporate bias-exchange metadynamics and parallel-tempering well-tempered metadynamics with CHARMM36m and CHARMM22* to explore the structural and thermodynamic characteristics of a short archetypal disordered sequence derived from a DEAD-box protein. The conformational landscapes emerging from our simulations are largely congruent across methods and force fields. Nevertheless, differences in fine details emerge from varying combinations of force-fields and sampling methods. For this protein, our analysis identifies features that help to explain the low propensity of this sequence to undergo self-association in vitro, which are common to all force-field/sampling method combinations. Overall, our work demonstrates the importance of using multiple force-field and sampling method combinations for accurate structural and thermodynamic information in the study of disordered proteins.

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“…Here, we propose and demonstrate the use of two protein force-fields compatible with three-point CHARMM-modified TIP3P water, namely, CHARMM36m and CHARMM22*, in combination with our chosen sampling methods. In particular, CHARMM36m showed improved accuracy in generating polypeptide backbone conformational ensembles for intrinsically disordered proteins 79,97 , despite the issue of over-compact structures and over-stabilized helices 76,98 . The "helix-coil-balanced" CHARMM22*, instead, is not only able to reproduce experimental native-state structure and proteins folding rate, but also shows good agreement with experimental secondary structure propensities and NMR chemical shifts for many disordered proteins 76,89,98 .…”

Section: Introductionmentioning

confidence: 99%

Modelling the structure and interactions of intrinsically disordered proteins with multiple-replica, metadynamics-based sampling methods and force-field combinations

Casalini

Arosio

et al. 2021

Preprint

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Intrinsically disordered proteins (IDPs) play a key role in many biological processes, including the formation of biomolecular condensates within cells. A detailed characterization of their configurational ensemble and structure-function paradigm is crucial for understanding their biological activity and for exploiting them as building blocks in material sciences. In this work, we incorporate bias-exchange metadynamics and parallel-tempering well-tempered metadynamics with CHARMM36m and CHARMM22* to explore the structural and thermodynamic characteristics of a short archetypal disordered sequence derived from a DEAD-box protein. The conformational landscapes emerging from our simulations are largely congruent across methods and forcefields. Nevertheless, differences in fine details emerge from varying forcefield/sampling method combinations. For this protein, our analysis identifies features that help to explain the low propensity of this sequence to undergo self-association in vitro, which can be common to all force-field/sampling method combinations. Overall, our work demonstrates the importance of using multiple force-field/enhanced sampling method combinations for accurate structural and thermodynamic information in the study of general disordered proteins.

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Performance of CHARMM36m with modified water model in simulating intrinsically disordered proteins: a case study

Cited by 20 publications

References 46 publications

Kirkwood–Buff-Derived Force Field for Peptides and Proteins: Philosophy and Development of KBFF20

Kirkwood–Buff-Derived Force Field for Peptides and Proteins: Philosophy and Development of KBFF20

Modeling the Structure and Interactions of Intrinsically Disordered Peptides with Multiple Replica, Metadynamics-Based Sampling Methods and Force-Field Combinations

Modelling the structure and interactions of intrinsically disordered proteins with multiple-replica, metadynamics-based sampling methods and force-field combinations

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