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Revolutionary new quantum chemical software for molecular simulations

Periodic Reporting for period 2 - QCLAB (Revolutionary new quantum chemical software for molecular simulations)

Reporting period: 2018-05-01 to 2019-09-30

Drug discovery and development is a very complex and multidisciplinary field connected to biology, chemistry and medical sciences. The process of discovery and development takes a 10-15 years long timespan and huge financial effort to see from start to success. There are a lot of factors and criteria that a drug candidate has to fulfill such as specificity, effectiveness, etc. During this period a screening are made on the possible drug candidates aiming to enhance its properties. On average only a few candidates remains from several millions of substances and will be approved to become marketable medicine.
It costs 2.44 billion EUR to introduce a new drug on average (Their costs of failures are around 1.3 billion EUR and are included). Reducing failures of candidates and speed up the screening process (currently takes 5 years) is the key to decrease the overall costs of drug R&D. According to our trial simulation, the identification, optimization and testing period and therefore its R&D and capital costs could be reduced radically thanks to the unique simulation tool developed by our team.
We aim to remove several obstacles from computer aided drug design to become real. These obstacles include the following: computational capacity, algorithmic efficiency, and physical models describing interatomic interactions. Our aim is to overcome the computational capacity induced limitations: resulting in faster simulation times for larger molecules and systems.
The BrianQC software system is a unique package which makes possible for high volume calculations to effectively run on GPU. Our modules include several methods including molecular mechanics and quantum chemistry. BrianQC enables simulations within feasible time frame that were unreachable formerly. It provides new possibilities with high accuracy and have better cost efficiency compared to the conventional solutions. Our simulation software has been tested by several research groups and researchers both in Europe and worldwide. With our software it is possible not only to ask but answer new questions in the field of large molecule and attachment of active substances simulations.
The project started in 2017 May and the first year have been very successful. There have been work done to our GPU based modules to speed up calculation and to be able to handle more precise simulations namely, our parallel integrator module is capable of efficiently simulating up to h-type orbitals on the GPU.
We proceed to increase the speed of our modules and extend the portion where our modules can be utilized. Additionally we managed to add a new type of calculation to the supported ones (density functional theory SCF-DFT). This method allows for more precise calculations and used more frequently than the SCF-HF method. Furthermore, parts in the simulation can be calculated on the CPU as well.
To be able to simulate extremely large systems a less compute intensive method has to be used together with QC methods. These methods are called molecular mechanics (MM). They are a classical approximations of the forces within a molecule like chemical bonds, electrostatic force, etc. Molecular mechanics is capable to simulate a few real world phenomenon happening on the molecular scale however it remains an approximation of the underlying processes. It is beneficial to combine the MM methods and quantum chemical methods into a layered approach. We have successfully implemented such a method called ONIOM. This method balances between the precision and computational cost effectively and can combine several different methods together.
During the second year several other features have been added to the software package. Tha min activities were the testing of the BrianQC package by early adopters. We have been in contact with several adopters and thanks to them a lot of problems have been eliminated from our product. Thanks to them we managed to uncover and fix these problems. As a result BrianQC finally reached the stage of a product and has been proven “flight ready” by the users.
All the development work has been supported by other activities in the field of marketing and communication. We have made efforts in these areas as well. We have carried out a number of communication activities (webpage: www.brianqc.com scientific journal publication, events, etc.) and as a result we have received quite a bit of interest from users and research groups who want to use BrianQC in their research activities.
The main needs of the pharmaceutical industry are as follows. Reduce the number of molecular candidates, decrease the failure rate by cheap simulation, and use less experiments in the first stage of the drug R&D.
a) Progress beyond the state of the art
We have made a commitment to enable fast and precise simulations by two features. The first one is the selected precise simulation method (QC is based on physical first principles) was made available to run on GPUs. The second one is the fact that our highly specialized framework makes the calculation of high impulse moment orbitals (like f, g and h) available.
These features make our project unique. The availability of these high impulse orbitals are necessary to be able to simulate chemical bond formation and breaking in biologically relevant molecules and systems.
In order to increase the performance of our simulator we added the CPU as a computing device as well. In this way both the GPU and the CPU cores are utilized as much as possible. This CPU-GPU hybrid is also a highly innovative solution in the field of QC.
b) expected results and impacts
The previously listed facts and results make available the usage of QC simulations as a powerful tool within the pharmaceutical industry. These simulations can achieve the desired precision, can work together with other simulation methods, available to a wide scale of systems, flexible and experimentally validated. The introduction of QC was blocked by the trendemous computational time that is reduced by two orders of magnitude with our software module. As a consequence the main economical benefit of our product is the shortening of the phase of basic research during pharmaceutical drug research. This means cheaper and faster time to market. The advantages of our simulation tool will consequently result more frequent launch of new, more efficient and cheaper medicines, which would bring a significant change especially for Europe’s aging society.
This figure shows a ball stick representation of the retroviral integraze protein of the HIV virus.
This figure shows a ball stick representation of a storage protein that we managed to simulate.
This figure shows the secondary structure of the retroviral integraze protein of the HIV virus.