The OPEP protein model: from single molecules, amyloid formation, crowding and hydrodynamics to DNA/RNA systems

Abstract

The OPEP coarse-grained protein model has been applied to a wide range of applications since its first release 15 years ago. The model, which combines energetic and structural accuracy and chemical specificity, allows the study of single protein properties, DNA-RNA complexes, amyloid fibril formation and protein suspensions in a crowded environment. Here we first review the current state of the model and the most exciting applications using advanced conformational sampling methods. We then present the current limitations and a perspective on the ongoing developments.

Multiscale simulation of molecular processes in cellular environments

“…A few successful force fields are available today to treat proteins and combinations of macromolecular entities, such as the Martini or other models [14][15][16][17]. In the last decade, we have been developing the optimized potential for efficient protein structure prediction (OPEP) force field as a result of intensive modelling and validation studies [11,[18][19][20][21][22][23][24][25]. The molecular model is able to reproduce accurately the secondary and tertiary folding of proteins, intermolecular aggregations, internal stability and motions and so forth.…”

“…Proline is an exception, with all its heavy atoms considered [18,19]. The implicit solvent OPEP energy function, which retains structural accuracy and chemical specificity, is defined as a sum of local, non-bonded and hydrogen bonding (H-bond) terms and all analytical expressions are given in references [11,20]. Notably, H-bonds between backbone atoms are modelled by twoand four-body potentials, rather than Coulomb interactions, and the interactions between ion pairs were derived from all-atom PMF calculations.…”

“…In a preliminary investigation reported in reference [11], the LBMD technique was tested to simulate a huge system composed of about 18 000 rat I proteins modelled using the OPEP force field. The excellent scalability of the method allowed allocation of the run on 18 000 GPU and reach a few tenths of nanoseconds.…”

“…the OPEP force field [11]), such that the secondary, tertiary and quaternary structures are well reproduced and (ii) by describing water as a dynamically responsive medium that obeys the laws of fluid dynamics and that is able to host the presence of embedded bodies (figure 1). Depending on the level of description of the biological process, the intramolecular flexibility of the macromolecules can be treated differently, from accurate standard intramolecular forces, including bonding, bending and torsional terms, to a cruder elastic network, up to a rigid body representation.…”

Communication: Multiple atomistic force fields in a single enhanced sampling simulation

“…This method is an extension of our previous work using coarsegrained protein and RNA force fields. 21,24 The simulation is performed by the ST method where the weight parameters are self-updated by the energy fluctuations of the system which induce the transitions between the temperatures and the force fields.…”