Zeolites are crystalline aluminosilicates with microporous structures and are known to catalyze a number of commercially significant transformation reactions. Aluminosilicates contains Al atoms replacing some of the Si atoms of the SiO 4 tetrahedra in zeolite frameworks, and the resulting net negative charge is balanced by protonation of O atoms. Such protons on the framework form Brønsted acid sites (BAS or bridged Si-O(H)-Al site) that trigger acid-base catalytic reactions and this plays a critical role in many of its applications in catalysis. Confinement effects of the zeolite might be also important for catalytic reactions. A zeolite containing BAS is defined as an "acidic" zeolite. Such acidic zeolites have widespread applications in industrial process, such as petroleum refining, cracking, isomerization, ion-exchange, alcohol dehydration, air pollution adsorber and alkylation of hydrocarbons. Natural gas is mainly composed of methane, which can be extracted from shale gas at a low cost. Methane is mainly burned or consumed for electricity generation, whereas a very small portion of it is used as a fuel. Direct chemical transformation of methane is highly energy demanding due to very high C-H bond energy (> 100 kcal mol ). The most cost-effective strategy for converting methane to useful chemicals is to convert it to syngas (CO + H 2 ) at high temperature, and then, via Fischer-Tropsch process the syngas is converted to other hydrocarbons or alcohols. This transformation is energy inefficient and costly. Hence, the activation of methane is one of the crucial steps in its industrial applications. The commercial transformation of small alkanes into branched alkanes using zeolite catalysts is another area of interest. Such catalytic reactions also involve solid acids and hydrogen transfer. How does a solid acid catalyst, such as acidic zeolite, could activate the C-H bonds of an alkane? Current understanding is that, these reactions proceed via proton transfer between alkane and the zeolites leading to the formation of reactive carbocation intermediate. The proton exchange reactions between an alkane and BAS in zeolites are also reported and they can help us to fundamentally understand the C-H bond activation mechanisms within the pores of zeolites. The protonated zeolites are known to activate the C-H bond of methane; see Figure . Two types of mechanisms are envisaged for the C-H bond activation in alkane ; (a) direct and (b) bimolecular. In the direct mechanism, the acidic proton in the zeolite is exchanged with one of the protons of an alkane molecule through carbonium ion intermediate, i.e., via the formation of a penta-coordinated carbocation. However, in the bimolecular mechanism, the alkane molecule dissociates one of the H atoms to the zeolite framework, forming an alkoxyl intermediate, which subsequently undergoes reactions with the other alkane molecules. In previous studies it has been already shown that higher alkanes follow the bimolecular mechanism, whereas the lower alkanes react via direct mechanistic pathway. Accurate computation of free energy of these chemical reactions is important toward understanding the catalytic process and to relate to experimental kinetic data. The proton exchange reaction of our interest (Figure ) can be considered as A+B type, where the two reactant species are not forming a bound complex in the reactant state. Methane is not bound on BAS at ambient and higher temperatures, it can diffuse through the pores of the zeolite. The pore diameters of the zeolites are 6.36 Å in H-ZSM-5 and 9.69 Å in H-MCM-22. Thus the reactant state is likely to have large entropic contribution. To include this entropy in the free energy estimate, one has to go beyond using any model partition functions such as that of quantum-harmonic oscillator and translation of free particle, considering the diffusive nature of the small molecule within the zeolite pore. Further, such reactions are carried out at high temperature in industry. Thus ab-initio molecular dynamics (AIMD) is the natural choice of the method to model such chemical reactions. However, due to the large size of the reactive pore in zeolites, it is challenging to study these reactions using AIMD. A pragmatic approach is to use the hybrid quantum mechanics and molecular mechanics (QM/MM) method. In this work, we applied QM/MM methodology using an in-house developed CPMD/GULP interface code, to investigate the proton transfer reaction mechanism. The half life of the reactions in question is typically ∼10 6 s at 300 K. On the other hand, AIMD simulations with density functional theory are limited to simulating ∼10 2 ps for systems containing hundreds of atoms using present day computers. To overcome this timescale bottleneck we accelerate the barrier crossing event by using enhance sampling MD techniques. In particular, we used the temperature accelerated sliced sampling (TASS) approach developed in our laboratory to simulate the proton exchange reaction and for computing the free energies. This method has an advantage that allows a control sampling of reaction free energy landscape of loosely bound reactant molecules. Sliced sampling allow an efficient sampling of the high dimensional free energy surface. Large number of collective variables can be considered for enhanced sampling. Various chemical and biological reactions have already been studied using the TASS method. H-MCM-22 zeolite, which contains a unique structure with both 10-membered ring and 12-membered ring systems, has been getting much attention for its commercial usage in many catalytic reactions. The high silica zeolite, H-ZSM-5 is comprised of the uniform medium-size pore and is widely studied due to its exceptional catalytic properties in petrochemical process and gas separation. We looked at the proton exchange reaction between CH 4 and H-ZSM-5, as well as, H-MCM-22 zeolites.