GROMACS Tutorial - TMD with NeqPCA

gromacs PCA 做自由能景观图 在文献中看到有人做自由能景观图,记录下自己的操作过程 参考http://www.kangsgo.com/49.html http://sobereva.com/73 https://www.zhihu.com/question/19895566 跑完动力学后蛋白比对 gmx trjconv -f md.xtc -s md.tpr -fit rot+trans -o mdfit.xtc 选择backbone 以及 system用于输出 然后生成协方差 gmx covar -s md.gro -f mdfi 阅读详情

Introduction

首先简单介绍一下TMD模拟,类似于SMD模拟(可以参考这篇教程),TMD 通过pull_coord1_type = constraint的设置,使用恒定拉力强制配体与蛋白质发生解结合,最终效果与SMD类似。

本教程基于 Multisecond ligand dissociation dynamics from atomistic simulations 1 第二个模拟体系 benzamidine-trypsin 编写,意在指导读者运行蛋白质-配体的模拟体系,以及 TMD(牵引动力学模拟)和后续 PCA 分析的进行。

[1] Wolf, S., Lickert, B., Bray, S. et al. Multisecond ligand dissociation dynamics from atomistic simulations. Nat Commun 11, 2918 (2020). https://doi.org/10.1038/s41467-020-16655-1

System Building

Generate Topology

首先我们需要获取 benzamidine-trypsin 晶体结构,前往RCSB下载3PTB的结构。随后将 trypsin 蛋白单独储存为 protein.pdb,将配体加氢后单独储存为 ligand.mol2(但是因为3PTB里面给的配体结构比较奇葩,加氢后氢的数量不一定对,因此建议前往PubChem下载3D结构的 .sdf 文件;然后手动对其到原配体位置后转存为 .mol2 文件,这一步可以在 PyMOL 里面完成,主要是为了后续合并文件时方便)。

对于配体文件:你可以通过你喜欢的方式获得它的参数,也可以按照这篇博文的方法完成,本文默认使用 Gaussain+Multiwfn+sobtop 先计算RESP后创建GAFF力场参数的方法创建配体参数。

计算RESP电荷,运行(<path_to_tut>是教程解压后的文件夹):

cd <path_to_tut>/lig_para

chmod +x RESP.sh 
./RESP.sh ligand.mol2 0

单核运行大概需要50分钟,随后就会得到 ligand.chg,随后利用 sobtop 创建力场参数(<path_to_sobtop>是你安装sobtop的文件夹):

cd <path_to_sobtop>
./sobtop

# 启动后输入:
<path_to_tut>/lig_para/ligand.mol2
2
<path_to_tut>/lig_para/ligand.gro
7
10
<path_to_tut>/lig_para/ligand.chg
0
1
2
4
<path_to_tut>/lig_para/ligand.top
<path_to_tut>/lig_para/ligand.itp

本教程使用的是 amber99sb-ildn 力场(当然你可以使用你喜欢而且合理的力场),但是由于我们新生成了配体的参数,需要将 ligand.itp 中 [ atomtypes ] 字段整合到力场的 ffnonbonded.itp 中(你只需要将他们剪切到 ffnonbonded.itp 中就行,但是本教程提供的文件中已经帮你整合好了,所以你只需要删除ligand.itp 中的 [ atomtypes ] 内容)。并且修改 [ moleculetype ] 字段下的名称为 MOL(为了方便后续操作),最终ligand.itp应该长这样:

; Created by Sobtop (http://sobereva.com/soft/sobtop) Version 1.0(dev3.1) on 2023-08-24

[ moleculetype ]
; name          nrexcl
MOL       3

[ atoms ]
;  Index   type   residue  resname   atom        cgnr     charge       mass
     1     nh         1      MOL     N             1   -0.98041913   14.006703
     2     n2         1      MOL     N             2   -0.94207571   14.006703
     3     ca         1      MOL     C             3   -0.00867452   12.010736
     4     ca         1      MOL     C             4   
GROMACS自由能景观图绘制全流程:从PCA分析到Origin 3D可视化(附避坑指南) 本文详细介绍了使用GROMACS绘制自由能景观图的全流程,涵盖从PCA分析、轨迹投影、自由能计算到Origin 3D可视化的完整步骤。重点解析了数据处理中的常见报错(如Origin矩阵转换错误)并提供根本解决方案,指导如何通过参数调优和插值方法(如Kriging)生成高质量、信息丰富的3D自由能景观图,助力深入理解生物分子的构象动力学与稳定性。 阅读详情

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深度学习工具包 DeepLearningToolbox

深度学习工具包Deprecation notice.-----This toolbox is outdated and no longer maintained.There are much better tools available for deep learning than this toolbox, e.g. [Theano](http://deeplearning.net/software/theano/), [torch](http://torch.ch/) or [tensorflow](http://www.tensorflow.org/)I would suggest you use one of the tools mentioned above rather than use this toolbox.Best, Rasmus.DeepLearnToolbox================A Matlab toolbox for Deep Learning.Deep Learning is a new subfield of machine learning that focuses on learning deep hierarchical models of data.It is inspired by the human brain's apparent deep (layered, hierarchical) architecture.A good overview of the theory of Deep Learning theory is[Learning Deep Architectures for AI](http://www.iro.umontreal.ca/~bengioy/papers/ftml_book.pdf)For a more informal introduction, see the following videos by Geoffrey Hinton and Andrew Ng.* [The Next Generation of Neural Networks](http://www.youtube.com/watch?v=AyzOUbkUf3M) (Hinton, 2007)* [Recent Developments in Deep Learning](http://www.youtube.com/watch?v=VdIURAu1-aU) (Hinton, 2010)* [Unsupervised Feature Learning and Deep Learning](http://www.youtube.com/watch?v=ZmNOAtZIgIk) (Ng, 2011)If you use this toolbox in your research please cite [Prediction as a candidate for learning deep hierarchical models of data](http://www2.imm.dtu.dk/pubdb/views/publication_details.php?id=6284)```@MASTERSTHESIS\{IMM2012-06284, author = "R. B. Palm", title = "Prediction as a candidate for learning deep hierarchical models of data", year = "2012",}```Contact: rasmusbergpalm at gmail dot comDirectories included in the toolbox-----------------------------------`NN/` - A library for Feedforward Backpropagation Neural Networks`CNN/` - A library for Convolutional Neural Networks`DBN/` - A library for Deep Belief Networks`SAE/` - A library for Stacked Auto-Encoders`CAE/` - A library for Convolutional Auto-Encoders`util/` - Utility functions used by the libraries`data/` - Data used by the examples`tests/` - unit tests to verify toolbox is workingFor references on each library check REFS.mdSetup-----1. Download.2. addpath(genpath('DeepLearnToolbox'));Example: Deep Belief Network---------------------```matlabfunction test_example_DBNload mnist_uint8;train_x = double(train_x) / 255;test_x = double(test_x) / 255;train_y = double(train_y);test_y = double(test_y);%% ex1 train a 100 hidden unit RBM and visualize its weightsrand('state',0)dbn.sizes = [100];opts.numepochs = 1;opts.batchsize = 100;opts.momentum = 0;opts.alpha = 1;dbn = dbnsetup(dbn, train_x, opts);dbn = dbntrain(dbn, train_x, opts);figure; visualize(dbn.rbm{1}.W'); % Visualize the RBM weights%% ex2 train a 100-100 hidden unit DBN and use its weights to initialize a NNrand('state',0)%train dbndbn.sizes = [100 100];opts.numepochs = 1;opts.batchsize = 100;opts.momentum = 0;opts.alpha = 1;dbn = dbnsetup(dbn, train_x, opts);dbn = dbntrain(dbn, train_x, opts);%unfold dbn to nnnn = dbnunfoldtonn(dbn, 10);nn.activation_function = 'sigm';%train nnopts.numepochs = 1;opts.batchsize = 100;nn = nntrain(nn, train_x, train_y, opts);[er, bad] = nntest(nn, test_x, test_y);assert(er < 0.10, 'Too big error');```Example: Stacked Auto-Encoders---------------------```matlabfunction test_example_SAEload mnist_uint8;train_x = double(train_x)/255;test_x = double(test_x)/255;train_y = double(train_y);test_y = double(test_y);%% ex1 train a 100 hidden unit SDAE and use it to initialize a FFNN% Setup and train a stacked denoising autoencoder (SDAE)rand('state',0)sae = saesetup([784 100]);sae.ae{1}.activation_function = 'sigm';sae.ae{1}.learningRate = 1;sae.ae{1}.inputZeroMaskedFraction = 0.5;opts.numepochs = 1;opts.batchsize = 100;sae = saetrain(sae, train_x, opts);visualize(sae.ae{1}.W{1}(:,2:end)')% Use the SDAE to initialize a FFNNnn = nnsetup([784 100 10]);nn.activation_function = 'sigm';nn.learningRate = 1;nn.W{1} = sae.ae{1}.W{1};% Train the FFNNopts.numepochs = 1;opts.batchsize = 100;nn = nntrain(nn, train_x, train_y, opts);[er, bad] = nntest(nn, test_x, test_y);assert(er < 0.16, 'Too big error');```Example: Convolutional Neural Nets---------------------```matlabfunction test_example_CNNload mnist_uint8;train_x = double(reshape(train_x',28,28,60000))/255;test_x = double(reshape(test_x',28,28,10000))/255;train_y = double(train_y');test_y = double(test_y');%% ex1 Train a 6c-2s-12c-2s Convolutional neural network %will run 1 epoch in about 200 second and get around 11% error. %With 100 epochs you'll get around 1.2% errorrand('state',0)cnn.layers = { struct('type', 'i') %input layer struct('type', 'c', 'outputmaps', 6, 'kernelsize', 5) %convolution layer struct('type', 's', 'scale', 2) %sub sampling layer struct('type', 'c', 'outputmaps', 12, 'kernelsize', 5) %convolution layer struct('type', 's', 'scale', 2) %subsampling layer};cnn = cnnsetup(cnn, train_x, train_y);opts.alpha = 1;opts.batchsize = 50;opts.numepochs = 1;cnn = cnntrain(cnn, train_x, train_y, opts);[er, bad] = cnntest(cnn, test_x, test_y);%plot mean squared errorfigure; 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Probability and Statistics - 4th edition

Probability and Statistics - 4th edition

上一篇: GROMACS Tutorial - dcTMD 估算非平衡状态的下自由能
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