Beta-phosphoglucomutase reaction using multidimensional Potential energy scans.

Introduction

In this tutorial, we will employ relaxed potential energy surface scans to simulate the reaction catalyzed by the enzyme β-phosphoglucomutase (PGMase). This enzyme facilitates the conversion of β-glucose-1,6-bisphosphate into β-glucose-6-phosphate, as illustrated in Figure 1. To achieve this, we will perform a simultaneous scan of two reaction coordinates:

The transfer of the phosphate group, characterized by the O1-P distance minus the P-O2 distance.
Proton transfer, defined by the H-O3 distance minus the O1-H distance.

Figure 1: Reaction scheme for the reaction of β-PGM complexed with β-G16BP. Adapted from: Marcos, E., Field, M. J., & Crehuet, R. (2010). Pentacoordinated phosphorus revisited by high‐level QM/MM calculations. Proteins: Structure, Function, and Bioinformatics, 78(11), 2405-2411.

This tutorial assumes that you are proficient in pruning a system using pDynamo/EasyHybrid and have the knowledge to accurately define and set up the Quantum Region for a hybrid QC/MM system.
At this point, we won't delve into the accuracy of the chosen Hamiltonian or the size of the Quantum Chemistry (QC) region; these aspects will be addressed in a later tutorial. Our current focus is on selecting a setup that allows us to complete the tutorial efficiently.

System Loading

First, load the system containing the PGMase enzyme and substrate into EasyHybrid (Figure 2). The previously prepared system is available in the file provided below:

phosphoglucomutase pkl file.

To open this file, navigate to: Main Menu > File > Open (Change the file type from ".easy" to ".pkl"). For more details check the user guide.

Figure 2: Enzyme + substrate complex loaded into EasyHybrid. The region previously determined to be quantum is presented in the form of balls and sticks.

Applying of PES Method

With the structures of the reactants and products properly sampled, we will now apply the NEB method to simulate the reaction.

Figure 3: . The same window can be accessed through the main menu by going to: simulation> Nudged Elastic Band (NEB).

With the structures of the reactants and products properly sampled, we will now apply the NEB method to simulate the reaction.

Figure 4: Enzyme + substrate complex loaded into EasyHybrid. The region previously determined to be quantum is presented in the form of balls and sticks.

With the structures of the reactants and products properly sampled, we will now apply the NEB method to simulate the reaction. It's worth n

Figure 4: To view the results obtained, simply go to File>Import Data... Select the format "pkl folder - pDynamo trajectory", folder containing the obtained trajectory and the log file (this is optional). also define the name of the new object that will be created (here called "Reaction").

With the structures of the reactants and products properly sampled, we will now apply the NEB method to simulate the reaction. It's worth

TYPE EasyHybrid-SCAN2D

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---------------------- Coordinate 1 - multiple-Distance ------------------------

ATOM1 = 3439 ATOM NAME1 = O1

ATOM2* = 3449 ATOM NAME2 = P'

ATOM3 = 134 ATOM NAME3 = OD1

NUMBER OF STEPS = 15 FORCE CONSTANT = 4000

DMINIMUM = -1.34881 MAX INTERACTIONS = 6000

STEP SIZE = 0.2000000 RMS GRAD = 0.1000000

Sigma atom1 - atom3 = 1.00000 Sigma atom3 - atom1 = -1.00000

--------------------------------------------------------------------------------

---------------------- Coordinate 2 - multiple-Distance ------------------------

ATOM1 = 166 ATOM NAME1 = OD2

ATOM2* = 167 ATOM NAME2 = HD2

ATOM3 = 3439 ATOM NAME3 = O1

NUMBER OF STEPS = 20 FORCE CONSTANT = 4000

DMINIMUM = -1.55232 MAX INTERACTIONS = 6000

STEP SIZE = 0.1500000 RMS GRAD = 0.1000000

Sigma atom1 - atom3 = 1.00000 Sigma atom3 - atom1 = -1.00000

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Frame i / j RCOORD-1 RCOORD-2 Energy

--------------------------------------------------------------------------------

DATA 0 0 -1.347591834094 -1.551533234158 -38585.938051806050

DATA 0 1 -1.347347256862 -1.403006117835 -38586.004159391261

DATA 0 2 -1.347401385495 -1.254045935152 -38584.882729596589

DATA 0 3 -1.347239826261 -1.104475639936 -38582.899727554148

DATA 0 4 -1.346737007947 -0.955151635399 -38580.066874046141

DATA 0 5 -1.346141517555 -0.803056933794 -38577.240889099558

DATA 0 6 -1.345546578997 -0.654504717606 -38576.003756701451

DATA 0 7 -1.345300629111 -0.506767152005 -38572.089576295744

DATA 0 8 -1.344979650414 -0.357592501914 -38566.285736090751

DATA 0 9 -1.344503939650 -0.207053752267 -38560.079205211405

DATA 0 10 -1.343917810508 -0.054388986381 -38556.428562353358

DATA 0 11 -1.343394037132 0.098321403003 -38555.469513713528

DATA 0 12 -1.342723740270 0.250853981420 -38558.314420720031

DATA 0 13 -1.342232064945 0.401622740040 -38562.842293509180

DATA 0 14 -1.341719712912 0.550967961655 -38567.802273128298

DATA 0 15 -1.341396027451 0.698042366123 -38570.122773680814

With the structures of the reactants and products properly sampled, we will now apply the NEB method to simulate the reaction. It's worth noting that this method offers a significant advantage over the reaction coordinate scans discussed in other tutorials. In NEB, there's no need to define a reaction coordinate; you only need the coordinates of the reactants and products. To access the NEB window, click on the icon shown in Figure 5, located on the toolbar of the main window.

Figure 5: Enzyme + substrate complex loaded into EasyHybrid. The region previously determined to be quantum is presented in the form of balls and sticks.

Figure 6: