Bovine Pancreatic Trypsin Inhibitor BPTI Simulations

Bovine Pancreatic Trypsin Inhibitor (BPTI) Simulations 

---

In periodic boimdary conditions, one possible way to avoid truncation of electrostatic interaction is to apply the so-called Particle Mesh Ewald (PME) method, which follows the Ewald summation method of calculating the electrostatic energy for a number of charges [27]. It was first devised by Ewald in 1921 to study the energetics of ionic crystals [28]. PME has been widely used for highly polar or charged systems. York and Darden applied the PME method already in 1994 to simulate a crystal of the bovine pancreatic trypsin inhibitor (BPTI) by molecular dynamics [29]. 

The details of many all-atom unfolding simulation studies have been summarized in several reviews [17,46,47]. These studies include unfolding simulations of a-lactalbumin, lysozyme, bovine pancreatic trypsin inhibitor (BPTI), barnase, apomyoglobin, [3-lacta-mase, and more. The advantage of these simulations is that they provide much more detailed information than is available from experiment. However, it should be stressed that there is still only limited evidence that the pathways and intermediates observed in the nanosecond unfolding simulations correlate with the intermediates observed in the actual experiments. 

We extrapolate from two simulations, the 10 ps simulation on bovine pancreatic trypsin inhibitor (BPTI) reported over twenty years ago [61] and the recent 1 gs simulation on the villin headpiece subdomain. [9] Each of these was a state-of-the-art simulation, using the best algorithms and the most powerful hardware available at the time. 

Another globular protein, bovine pancreatic trypsin inhibitor (BPTI), has also been treated by the build-up procedure however, because of a limitation on computer time when the calculation on this protein was carried out, a limited set of simulated NMR distance constraints (taken from the known X-ray structure225) was used226-227 to reduce the number of conformations... 

Verification of the structural and dynamic behavior of proteins predicted by simulations has been possible by comparison with experiment. Approximate agreement between the average structure obtained in the first simulation of a protein (McCammon et al. 1977), that of bovine pancreatic trypsin inhibitor (BPTI), and the... 

To illustrate the solvent effect on the average structure of a protein, we describe results obtained from conventional molecular dynamics simulations with periodic boundary conditions.92,193 This method is well suited for a study of the global features of the structure for which other approaches, such as stochastic boundary simulation methods, would not be appropriate. We consider the bovine pancreatic trypsin inhibitor (BPTI) in solution and in a crystalline environment. A simulation was carried out for a period of 25 ps in the presence of a bath of about 2500 van der Waals particles with a radius and well depth corresponding to that of the oxygen atom in ST2 water.193 The crystal simulation made use of a static crystal environment arising from the surrounding protein molecules in the absence of solvent. These studies, which were the first application of simulation methods to determine the effect of the environment on a protein, used simplified representations of the surround-... 

The simulations reported in the paper dealt with bovine pancreatic trypsin inhibitor (BPTI), a small (58 amino acid) protease inhibitor whose structure is stabilized by three disulfide crosslinks. The simulation began with a set of X-ray coordinates and zero velocities, and ran 100 steps of numerical integration of Newton s equations of motion, with each time step being about 1 fs. Since the X-ray coordinates did not correspond to a minimum of... 

Quasi-harmonic analysis is the computation of the normal modes of a molecule from atomic displacements generated by a molecular dynamics simulation. In this case, the atomic coordinate fluctuations are inversely related to the force constants, which are the second derivatives of the potential function. This formulation allows anharmonic motions, arising either from continuous diffusive motion or from transitions between wells, to be included implicitly within a harmonic representation, Brooks and co-workers " have carried out a comparison of different approaches to calculating the harmonic and quasiharmonic normal modes for the protein bovine pancreatic trypsin inhibitor (BPTI) with different force field and simulation models, Yet another approach, called essential dynamics, differs from quasi-harmonic analysis in that the atomic masses are not considered and motion is not reduced to a harmonic form, ... 

Bovine pancreatic trypsin inhibitor (BPTI) has been a widely used model protein for study. There is a good deal of both experiment and computational study on this system. There are a number of crystal and NMR structures of the native, oxidized form of BPTI. The protein with the disulfide linkage reduced, an presumably unfolded state, has been the subject of a number of experimental studies and previous simulations in our group. ... 

Simulations of BPTI (bovine pancreatic trypsin inhibitor) in van der Waals solvents have been reported [74, 75], the density and molecular size were chosen to simulate those of water. More realistic water representations were used in further simulations [18, 76, 77]. Avian pancreatic polypeptide hormone in crystal and in aqueous solution has been reported by Kruger [78]. These studies tend to indicate that the calculations in vacuo represent fairly correctly the motion of the protein core, while exposed sidechains react more strongly to solvent effects. 

---